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Acta Ophthalmologica Mar 2024Glaucoma is currently considered one of the leading causes of severe visual impairment and blindness worldwide. Topical medical therapy represents the treatment of... (Review)
Review
Glaucoma is currently considered one of the leading causes of severe visual impairment and blindness worldwide. Topical medical therapy represents the treatment of choice for many glaucoma patients. Introduction of latanoprost, 25 years ago, with an entirely new mechanism of action from that of the antiglaucoma drugs used up to that time was a very important milestone. Since then, due mainly to their efficacy, limited systemic side effects and once daily dosing, prostaglandin analogues (PGAs) have become as the first-choice treatment for primary open-angle glaucoma. PGAs are in general terms well tolerated, although they are associated with several mild to moderate ocular and periocular adverse events. Among them, conjunctival hyperemia, eyelash changes, eyelid pigmentation, iris pigmentation and hypertrichosis around the eyes are the most prevalent. The objective of this paper is to review the role of PGAs in the treatment of glaucoma over the 25 years since the launch of Latanoprost and their impact on clinical practice outcomes.
Topics: Humans; Latanoprost; Glaucoma, Open-Angle; Prostaglandins F, Synthetic; Antihypertensive Agents; Glaucoma; Prostaglandins, Synthetic; Ocular Hypertension; Intraocular Pressure
PubMed: 37350260
DOI: 10.1111/aos.15725 -
Reproductive Sciences (Thousand Oaks,... Aug 2023Dysmenorrhea is a prevalent gynecological disease among women at reproductive age. It is classified as the primary dysmenorrhea and the secondary dysmenorrhea according... (Review)
Review
Dysmenorrhea is a prevalent gynecological disease among women at reproductive age. It is classified as the primary dysmenorrhea and the secondary dysmenorrhea according to the etiology. The primary dysmenorrhea is caused by uterine hypercontraction without any identifiable pelvic lesions, while the secondary dysmenorrhea is incurred by gynecological disorder with pelvic organic lesions. However, the underlying mechanism of dysmenorrhea is not completely clear. Animal models of dysmenorrhea, especially mouse and rat model, are helpful to explore the pathophysiological mechanism of dysmenorrhea, clarify the therapeutic effect of compounds, and guide clinical treatment. The murine model of primary dysmenorrhea is commonly induced by oxytocin or prostaglandin F, while the secondary dysmenorrhea murine model was further created by injecting oxytocin on the basis of the established primary disease model. This review summarizes the current progress of dysmenorrhea models in rodent, including experimental methods, corresponding evaluation indexes, and the advantages and disadvantages of various murine dysmenorrhea models, in order to provide a reference for the selection of murine dysmenorrhea models and the further study of the pathophysiological mechanism of dysmenorrhea.
Topics: Humans; Female; Mice; Rats; Animals; Dysmenorrhea; Oxytocin; Disease Models, Animal; Uterus; Dinoprost
PubMed: 37010703
DOI: 10.1007/s43032-023-01220-0 -
JCI Insight Dec 2023Idiopathic pulmonary fibrosis (IPF) is a chronic parenchymal lung disease characterized by repetitive alveolar cell injury, myofibroblast proliferation, and excessive...
Idiopathic pulmonary fibrosis (IPF) is a chronic parenchymal lung disease characterized by repetitive alveolar cell injury, myofibroblast proliferation, and excessive extracellular matrix deposition for which unmet need persists for effective therapeutics. The bioactive eicosanoid, prostaglandin F2α, and its cognate receptor FPr (Ptgfr) are implicated as a TGF-β1-independent signaling hub for IPF. To assess this, we leveraged our published murine PF model (IER-SftpcI73T) expressing a disease-associated missense mutation in the surfactant protein C (Sftpc) gene. Tamoxifen-treated IER-SftpcI73T mice developed an early multiphasic alveolitis and transition to spontaneous fibrotic remodeling by 28 days. IER-SftpcI73T mice crossed to a Ptgfr-null (FPr-/-) line showed attenuated weight loss and gene dosage-dependent rescue of mortality compared with FPr+/+ cohorts. IER-SftpcI73T/FPr-/- mice also showed reductions in multiple fibrotic endpoints for which administration of nintedanib was not additive. Single-cell RNA-Seq, pseudotime analysis, and in vitro assays demonstrated Ptgfr expression predominantly within adventitial fibroblasts, which were reprogrammed to an "inflammatory/transitional" cell state in a PGF2α /FPr-dependent manner. Collectively, the findings provide evidence for a role for PGF2α signaling in IPF, mechanistically identify a susceptible fibroblast subpopulation, and establish a benchmark effect size for disruption of this pathway in mitigating fibrotic lung remodeling.
Topics: Mice; Animals; Dinoprost; Fibroblasts; Idiopathic Pulmonary Fibrosis; Fibrosis; Population Dynamics
PubMed: 37934604
DOI: 10.1172/jci.insight.172977 -
Frontiers in Endocrinology 2023Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in...
INTRODUCTION
Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in uterine tissues. This includes increased leukocyte infiltration, and subsequent increase in chemokine and cytokine levels, activation of pro-inflammatory transcription factors as NF-κB and increased prostaglandin synthesis. Prostaglandin F2α (PGF2α) is one of the myometrial activators and stimulators.
METHODS
Here we investigated the role of PGF2α in pro-inflammatory signalling pathways in human myometrial cells isolated from term non-labouring uterine tissue. Primary myometrial cells were treated with G protein inhibitors, calcium chelators and/or PGF2α. Nuclear extracts were analysed by TranSignal cAMP/Calcium Protein/DNA Array. Whole cell protein lysates were analysed by Western blotting. mRNA levels of target genes were analysed by RT-PCR.
RESULTS
The results show that PGF2α increases inflammation in myometrial cells through increased activation of NF-κB and MAP kinases and increased expression of COX-2. PGF2α was found to activate several calcium/cAMP-dependent transcription factors, such as CREB and C/EBP-β. mRNA levels of NF-κB-regulated cytokines and chemokines were also elevated with PGF2α stimulation. We have shown that the increase in PGF2α-mediated COX-2 expression in myometrial cells requires coupling of the FP receptor to both Gαq and Gαi proteins. Additionally, PGF2α-induced calcium response was also mediated through Gαq and Gαi coupling.
DISCUSSION
In summary, our findings suggest that PGF2α-induced inflammation in myometrial cells involves activation of several transcription factors - NF-κB, MAP kinases, CREB and C/EBP-β. Our results indicate that the FP receptor signals via Gαq and Gαi coupling in myometrium. This work provides insight into PGF2α pro-inflammatory signalling in term myometrium prior to the onset of labour and suggests that PGF2α signalling pathways could be a potential target for management of preterm labour.
Topics: Infant, Newborn; Female; Humans; Dinoprost; NF-kappa B; Calcium; Premature Birth; Cyclooxygenase 2; Myometrium; Inflammation; Obstetric Labor, Premature; Cytokines; RNA, Messenger
PubMed: 37547305
DOI: 10.3389/fendo.2023.1150125 -
Reproduction in Domestic Animals =... Sep 2023Canine pregnancy relies on luteal steroidogenesis for progesterone (P4) production. The canine placenta responds to P4, depending on the nuclear P4 receptor (PGR). This... (Review)
Review
Canine pregnancy relies on luteal steroidogenesis for progesterone (P4) production. The canine placenta responds to P4, depending on the nuclear P4 receptor (PGR). This has sparked interest in investigating the interaction between ovarian luteal steroids and the placenta in dogs. Canine placentation is characterized by restricted (shallow) trophoblast invasion, making the dog an interesting model for studying decidua-derived modulation of trophoblast invasion, compared with the more invasive (hemochorial) placentation. The PGR is expressed in maternally derived decidual cells and plays a crucial role in feto-maternal communication during pregnancy maintenance. Understanding PGR-mediated signalling has clinical implications for improving reproductive performance control in dogs. Altering the PGR signalling induces the release of PGF2α from the foetal trophoblast, hindering placental homeostasis, which can also be achieved with antigestagens like aglepristone. Consequently, luteolysis, both natural and antigestagen-induced, involves apoptosis, vascular lesion, and immune cell infiltration in the placenta, resulting in placentolysis and foetal membranes expulsion. Our laboratory developed the immortalized dog uterine stromal (DUS) cell line to study canine-specific decidualization. We study canine reproduction by observing physiological processes and investigating evidence-based mechanisms of decidualization and feto-maternal interaction. Our focus on morphology, function and molecular aspects enhances understanding and enables targeted and translational studies.
Topics: Female; Pregnancy; Dogs; Animals; Placenta; Ovary; Apoptosis; Corpus Luteum; Dinoprost
PubMed: 37724655
DOI: 10.1111/rda.14443 -
International Journal of Dermatology Sep 2023
Topics: Humans; Latanoprost; Eye; Lichen Planus; Drug Eruptions; Ophthalmic Solutions; Lichenoid Eruptions; Antihypertensive Agents; Prostaglandins F, Synthetic
PubMed: 36732607
DOI: 10.1111/ijd.16602 -
Biology of Reproduction Sep 2023Cyclic regression of the ovarian corpus luteum, the endocrine gland responsible for progesterone production, involves rapid matrix remodeling. Despite fibroblasts in...
Cyclic regression of the ovarian corpus luteum, the endocrine gland responsible for progesterone production, involves rapid matrix remodeling. Despite fibroblasts in other systems being known for producing and maintaining extracellular matrix, little is known about fibroblasts in the functional or regressing corpus luteum. Vast transcriptomic changes occur in the regressing corpus luteum, among which are reduced levels of vascular endothelial growth factor A (VEGFA) and increased expression of fibroblast growth factor 2 (FGF2) after 4 and 12 h of induced regression, when progesterone is declining and the microvasculature is destabilizing. We hypothesized that FGF2 activates luteal fibroblasts. Analysis of transcriptomic changes during induced luteal regression revealed elevations in markers of fibroblast activation and fibrosis, including fibroblast activation protein (FAP), serpin family E member 1 (SERPINE1), and secreted phosphoprotein 1 (SPP1). To test our hypothesis, we treated bovine luteal fibroblasts with FGF2 to measure downstream signaling, type 1 collagen production, and proliferation. We observed rapid and robust phosphorylation of various signaling pathways involved in proliferation, such as ERK, AKT, and STAT1. From our longer-term treatments, we determined that FGF2 has a concentration-dependent collagen-inducing effect, and that FGF2 acts as a mitogen for luteal fibroblasts. FGF2-induced proliferation was greatly blunted by inhibition of AKT or STAT1 signaling. Our results suggest that luteal fibroblasts are responsive to factors that are released by the regressing bovine corpus luteum, an insight into the contribution of fibroblasts to the microenvironment in the regressing corpus luteum.
Topics: Animals; Cattle; Female; Cell Proliferation; Collagen; Corpus Luteum; Dinoprost; Fibroblast Growth Factor 2; Fibroblasts; Luteolysis; Progesterone; Proto-Oncogene Proteins c-akt; Vascular Endothelial Growth Factor A
PubMed: 37283496
DOI: 10.1093/biolre/ioad065 -
Theriogenology Mar 2024Year 2023 is the 100-year anniversary of the discovery in guinea pigs that the lifespan of the corpus luteum (CL) is controlled by the uterus. The CL is the gatekeeper... (Review)
Review
Year 2023 is the 100-year anniversary of the discovery in guinea pigs that the lifespan of the corpus luteum (CL) is controlled by the uterus. The CL is the gatekeeper between two fundamental reproductive events - the estrous cycle and pregnancy. Uteroluteal research for the initial 33 years was productive but limited to laboratory species until the inclusion of farm animals in 1956. In the early 1960s, it was found that uterine luteolysin in sows travels unilaterally from a uterine horn to the adjacent CL which likely accounted for the heyday of uteroluteal research in the 1960s-70s. The luteolytic properties of PGF2α were demonstrated in rats in 1969. In 1971, (1) surgical separation of the lengthwise adherence between the uteroovarian vein and ovarian artery interfered with luteolysis in ewes, (2) species with primarily unilateral vs systemic uterine-induced luteolysis have a strong vs an absent or weak unilateral venoarterial transfer pathway, and (3) vascular infusions identified PGF2α as a uterine luteolysin. Vascular and PGF2α studies were beginning to merge. In 1973, a venoarterial pathway was firmly demonstrated in ewes and later in heifers by surgical anastomosis of a uterine vein or ovarian artery from a uterine-intact side to the corresponding vessel on the unilaterally hysterectomized side. More recent studies described how prostaglandins likely transfer through the walls of uterine and ovarian vessels using concentration gradients in sows and a prostaglandins transporter system in cows.
Topics: Pregnancy; Animals; Female; Cattle; Sheep; Swine; Rats; Guinea Pigs; Luteolysis; Dinoprost; Corpus Luteum; Uterus; Mammals
PubMed: 38266370
DOI: 10.1016/j.theriogenology.2024.01.014 -
Archives of Dermatological Research Nov 2023In the recent decades, prostaglandins were recommended as a new therapeutic modality of stable vitiligo with promising efficacy. Therefore, we designed the current work...
In the recent decades, prostaglandins were recommended as a new therapeutic modality of stable vitiligo with promising efficacy. Therefore, we designed the current work to compare the significance of two different subtypes of prostaglandins [prostaglandin E2 (PGE2) versus prostaglandin F2 alpha (PGF2α)], assisted with NB-UVB phototherapy, in treatment of stable vitiligo. This study was conducted on 30 patients with stable non-segmental vitiligo. Three approximately similar vitiliginous areas were chosen in each patient and assigned into 3 groups. Each group treated with intradermal injection of either PGE2 (group I), PGF2α (group II), or saline as placebo (group III) at frequency once/week for 12 weeks. Concomitantly, all groups received NB-UVB phototherapy twice weekly for 3 months. The outcomes of this study discovered that the therapeutic efficacy of intradermal injection of either PGE2 or PGF2α assisted with NB-UVB phototherapy was comparable with non-significant difference between them in spite of being significantly higher than NB-UVB alone. However, there were a significantly earlier onset of repigmentation and higher degree of satisfaction regarding areas treated with PGE2 than those treated with PGF2α. In conclusion, both PGF2α and PGE2 intradermal injection could be considered as quite simple and affordable techniques in the treatment of stable vitiligo with no reported side effects and good patient satisfaction.
Topics: Humans; Dinoprostone; Dinoprost; Vitiligo; Hypopigmentation; Prostaglandins; Ultraviolet Therapy
PubMed: 37594537
DOI: 10.1007/s00403-023-02700-8 -
Journal of Neurosurgery Sep 2023Delayed cerebral ischemia (DCI) is a serious complication of aneurysmal subarachnoid hemorrhage (aSAH), which is responsible for significant death and disability. The...
OBJECTIVE
Delayed cerebral ischemia (DCI) is a serious complication of aneurysmal subarachnoid hemorrhage (aSAH), which is responsible for significant death and disability. The dynamic balance between the production and elimination of reactive oxygen species (ROS) in patients with DCI is suspected be shifted to favor ROS formation. The authors assessed the relationship between F2-isoprostanes (F2-IsoPs), oxidative stress biomarkers, and glucose-6-phosphate dehydrogenase (G6PD), which are responsible for nicotinamide adenine dinucleotide phosphate (NADPH) production for glutathione system function, with post-aSAH DCI.
METHODS
The authors assessed 45 aSAH patients for F2-IsoP and G6PD concentration using commercial ELISA on days 2, 4, and 6 after aSAH. The authors examined the correlation between plasma F2-IsoP and G6PD concentrations and clinical factors with DCI occurrence and aSAH outcome.
RESULTS
Expectedly, the most important clinical predictors of DCI were Hunt and Hess grade and modified Fisher (mFisher) grade. Plasma F2-IsoP and G6PD concentrations were greater in aSAH patients than the control group (p < 0.01). F2-IsoP concentrations were greater and G6PD concentrations were lower in patients with DCI than those without (p < 0.01). Plasma F2-IsoP and G6PD concentrations on day 2 were correlated with DCI occurrence (p < 0.01). Plasma F2-IsoP concentrations on days 2 and 6 were correlated with outcome at 1 and 12 months (p < 0.01).
CONCLUSIONS
Decreased G6PD indirectly informs the reduced antioxidant response, especially for the glutathione system. G6PD concentration was lower in patients with DCI than those without, which may explain the increased F2-IsoP concentrations. mFisher grade, plasma F2-IsoP concentration, and G6PD concentration on day 2 after aSAH, in combination, may serve as predictors of DCI. Further research is necessary to investigate the therapeutic utility of F2-IsoPs and antioxidants in clinical practice.
Topics: Humans; Subarachnoid Hemorrhage; Dinoprost; Glucosephosphate Dehydrogenase; Reactive Oxygen Species; Prospective Studies; Brain Ischemia; Cerebral Infarction; Glutathione
PubMed: 36640097
DOI: 10.3171/2022.12.JNS222332