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Biomedicine & Pharmacotherapy =... Sep 2022The objectives of this study were to investigate the antithrombotic effect and physiological mechanism of okanin, a flavonoid monomer in Coreopsis tinctoria Nutt. The...
The objectives of this study were to investigate the antithrombotic effect and physiological mechanism of okanin, a flavonoid monomer in Coreopsis tinctoria Nutt. The antithrombotic effects of okanin were determined by the anticoagulant activity test in vitro and in vivo, the venous thrombosis and arterial thrombosis test in rats. To study the antithrombotic physiological mechanisms of okanin, UV spectrophotometer and enzyme-linked immunosorbent assay (ELISA) were used to determine the effects of three concentrations of okanin on the contents of 6-keto-prostaglandin F1α (6-Keto-PGF), thromboxane B (TXB), endothelin-1 (ET-1), antithrombin III (AT-Ⅲ), protein C (PC) and von willebrand factor (vWF) in the plasma of rats with arterial thrombosis; ELISA was used to detect the effects of okanin on the contents of plasminogen (PLG), tissue plasminogen activator (t-PA) and type-1 plasminogen activator inhibitor (PAI-1) in the plasma of mice and Chinese white rabbits. The results showed that okanin could prolong the coagulation time in vitro and in vivo of animals (P < 0.01 in the high dose group) and the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) of human venous blood (ATPP of medium dose group P < 0.01; PT, TT P < 0.05. P < 0.01 in the high dose group); inhibit the maximum platelet aggregation rate of rabbits (P < 0.05 in the low dose group; P < 0.01 in the medium and high dose groups), decrease the dry and wet weight of venous thrombosis and the wet weight of common carotid artery thrombosis in rats (low dose group, P < 0.05; medium and high dose groups, P < 0.01); increase the levels of 6-Keto-PGF, AT-Ⅲ, PLG and t-PA in animal plasma; decrease the levels of TXB, ET-1, vWF and PAI- in animal plasma. It is concluded that okanin can significantly inhibit thrombosis, and its physiological mechanisms were related to affecting the activation of related coagulation factors in endogenous and exogenous coagulation pathways, affecting the physiological characteristics of platelets, repairing damaged vascular endothelial cells and enhancing the activity of the fibrinolytic system.
Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anticoagulants; Chalcones; Endothelial Cells; Fibrinolytic Agents; Humans; Rabbits; Rats; Thrombosis; Tissue Plasminogen Activator; von Willebrand Factor
PubMed: 35785699
DOI: 10.1016/j.biopha.2022.113358 -
Journal of Animal Science Jan 2023This review discusses endocrine and functional changes during the transition from late gestation to lactation that are related to the production of colostrum in... (Review)
Review
This review discusses endocrine and functional changes during the transition from late gestation to lactation that are related to the production of colostrum in different mammalian species. Species covered in this article include ungulate species (cattle, sheep, goats, pigs, horses), rodents (rat, mouse), rabbits, and carnivores (cats, dogs), as well as humans. An immediate availability of high quality colostrum for the newborn after birth is crucial in species where a transfer of immunoglobulins (Ig) does not or only partially occur via the placenta during pregnancy. Declining activity of gestagens, in most species progesterone (P4), is crucial at the end of pregnancy to allow for the characteristic endocrine changes to initiate parturition and lactation, but the endocrine regulation of colostrogenesis is negligible. Both, the functional pathways and the timing of gestagen withdrawal differ considerably among mammalian species. In species with a sustaining corpus luteum throughout the entire pregnancy (cattle, goat, pig, cat, dog, rabbit, mouse, and rat), a prostaglandin F2α (PGF2α)-induced luteolysis shortly before parturition is assumed to be the key event to initiate parturition as well as lactogenesis. In species where the gestagen production is taken over by the placenta during the course of gestation (e.g., sheep, horse, and human), the reduction of gestagen activity is more complex, as PGF2α does not affect placental gestagen production. In sheep the steroid hormone synthesis is directed away from P4 towards estradiol-17β (E2) to achieve a low gestagen activity at high E2 concentrations. In humans the uterus becomes insensitive to P4, as parturition occurs despite still high P4 concentrations. However, lactogenesis is not completed as long as P4 concentration is high. Early colostrum and thus Ig intake for immune protection is not needed for the human newborn which allows a delayed onset of copious milk secretion for days until the placenta expulsion causes the P4 drop. Like humans, horses do not need low gestagen concentrations for successful parturition. However, newborn foals need immediate immune protection through Ig intake with colostrum. This requires the start of lactogenesis before parturition which is not fully clarified. The knowledge of the endocrine changes and related pathways to control the key events integrating the processes of colostrogenesis, parturition, and start of lactation are incomplete in many species.
Topics: Pregnancy; Female; Swine; Cattle; Humans; Rats; Horses; Animals; Rabbits; Sheep; Dogs; Mice; Progestins; Dinoprost; Placenta; Parturition; Colostrum; Progesterone; Rodentia
PubMed: 37158662
DOI: 10.1093/jas/skad146 -
International Journal of Molecular... Apr 2023Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the...
Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the pathogenesis of Graves' ophthalmopathy (GO) involves the excessive adipogenesis of the orbital tissues. The present study aimed to determine the therapeutic effects and underlying mechanisms of PGF2α on adipocyte differentiation. In this study primary cultures of orbital fibroblasts (OFs) from six patients with GO were established. Immunohistochemistry, immunofluorescence, and Western blotting (WB) were used to evaluated the expression of the F-prostanoid receptor (FPR) in the orbital adipose tissues and the OFs of GO patients. The OFs were induced to differentiate into adipocytes and treated with different incubation times and concentrations of PGF2α. The results of Oil red O staining showed that the number and size of the lipid droplets decreased with increasing concentrations of PGF2α and the reverse transcription-polymerase chain reaction (RT-PCR) and WB of the peroxisome proliferator-activated receptor γ (PPARγ) and fatty-acid-binding protein 4 (FABP4), both adipogenic markers, were significantly downregulated via PGF2α treatment. Additionally, we found the adipogenesis induction of OFs promoted ERK phosphorylation, whereas PGF2α further induced ERK phosphorylation. We used Ebopiprant (FPR antagonist) to interfere with PGF2α binding to the FPR and U0126, an Extracellular Signal-Regulated Kinase (ERK) inhibitor, to inhibit ERK phosphorylation. The results of Oil red O staining and expression of adipogenic markers showed that blocking the receptor binding or decreasing the phosphorylation state of the ERK both alleviate the inhibitory effect of PGF2a on the OFs adipogenesis. Overall, PGF2α mediated the inhibitory effect of the OFs adipogenesis through the hyperactivation of ERK phosphorylation via coupling with the FPR. Our study provides a further theoretical reference for the potential application of PGF2α in patients with GO.
Topics: Humans; Dinoprost; Adipogenesis; Extracellular Signal-Regulated MAP Kinases; Graves Ophthalmopathy; Fibroblasts; Cells, Cultured
PubMed: 37108173
DOI: 10.3390/ijms24087012 -
Animal : An International Journal of... May 2023This manuscript reviews the mechanisms that maintain the corpus luteum (CL) of pregnancy in ruminants. In mammals, ovulation and luteinization of the remaining cells in... (Review)
Review
This manuscript reviews the mechanisms that maintain the corpus luteum (CL) of pregnancy in ruminants. In mammals, ovulation and luteinization of the remaining cells in the CL are due to a surge in Luteinizing Hormone (LH). In cattle, continued secretion of pulses of LH is essential for full development and function of the CL during the estrous cycle (LH pulses), however, the few studies on the CL after d20 of pregnancy do not indicate that LH is essential for maintaining the CL of pregnancy. The first essential step in maintaining the CL of pregnancy in ruminants is overcoming the mechanisms that cause regression of the CL in non-pregnant ruminants (d18-25 in cattle; d13-21 in sheep). These mechanisms have a uterine component involving oxytocin-induced prostaglandin F2α (PGF2A) pulses and a luteal component involving decreased progesterone production and luteal cell death. There is a critical role for embryonic interferon-tau (IFNT) in suppressing the uterine secretion of PGF2A during early pregnancy (d13-21 in sheep; d16-25 in cattle) and preventing luteolysis. There are also effects of IFNT on the expression of interferon-stimulated genes in other tissues including the CL but the physiologic role of these interferon-stimulated genes is not yet clear. After the IFNT period, there is another mechanism that maintains the CL of pregnancy in ruminants since embryonic IFNT is inhibited as attachment occurs and trophoblastic binucleate/giant cells begin secretion of pregnancy-associated glycoproteins. The second mechanism for luteal maintenance has not yet been defined but acts in a local manner (ipsilateral to pregnancy), and remains functional from d25 until just before parturition. The most likely mechanisms mediating later maintenance of the CL of pregnancy are increased uterine blood flow or decreased prostaglandin transporter expression in the utero-ovarian vasculature, preventing PGF2A reaching the CL. Finally, implications of these ideas on pregnancy loss in cattle are explored, highlighting the importance of inappropriate regression of the CL of pregnancy as a mechanism for pregnancy loss in cattle.
Topics: Pregnancy; Female; Cattle; Sheep; Animals; Corpus Luteum; Ruminants; Progesterone; Luteolysis; Ovary; Luteinizing Hormone; Dinoprost
PubMed: 37567676
DOI: 10.1016/j.animal.2023.100827 -
Veterinary Research Communications Dec 2022To determine the effect of the combination of melatonin implants and prostaglandin (PG) F2α on reproductive performance in the late breeding season (Dec at the northern...
To determine the effect of the combination of melatonin implants and prostaglandin (PG) F2α on reproductive performance in the late breeding season (Dec at the northern hemisphere), 500 Lacaune ewes were divided into four groups. On day 0 (7 Nov), 150 ewes were treated with a melatonin (M) implant. From that group, 64 ewes (M + 1PGF group) were injected with 10-mg prostaglandin (PG) F2α 34 d after melatonin implantation (11 Dec). The remaining 86 ewes (M group) were treated with melatonin, only. Another group of 75 ewes (2PGF group) was treated with double injection of PGF2α (9 days between the first and second application) (2 and 11 Dec), and 75 non-treated ewes (C group) were the control group. The remaining 200 ewes of the flock were not considered in the study. Rams (n = 23) were introduced on 11 Dec. The percentage of prolificacy, lambing and fecundity rates were calculated. Lambing rate did not differ among groups (M: 79%; M + 1PGF: 78%; 2PGF: 69%; C: 71%). The M + 1PGF group had a higher % of prolificacy than the 2PGF group (P < 0.10) and the C group (P = 0.06) (M: 1.65 ± 0.07; M + 1PGF: 1.74 ± 0.09; 2PGF: 1.54 ± 0.08; C: 1.54 ± 0.07 lambs/lambing) (P < 0.05), and a higher fecundity than the 2PGF group (P < 0.05) and the C group (P < 0.10) (M: 1.30 ± 0.09; M + 1PGF: 1.36 ± 0.11; 2PGF: 1.07 ± 0.10; C: 1.08 ± 0.09 lambs/ewe). Ewes implanted with melatonin had significantly higher prolificacy (1.69 ± 0.06 lambs/lambing) (P < 0.05) and fecundity (1.33 ± 0.07 lambs/ewe) (P = 0.01) than did ewes that did not receive melatonin (1.54 ± 0.04 and 1.08 ± 0.04, resp.). In conclusion, melatonin implants increased the number of lambs born per ewe in a late-autumn mating season, and the effect was greatest if it was given in combination with PGF2α administration at ram introduction.
Topics: Sheep; Animals; Female; Seasons; Dinoprost; Melatonin; Reproduction; Prostaglandins
PubMed: 36018475
DOI: 10.1007/s11259-022-09990-9 -
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 -
Indian Journal of Ophthalmology Dec 2023To investigate the intraocular pressure (IOP) lowering effect of topical preserved tafluprost 0.0015% in a tertiary hospital setting in India.
OBJECTIVE
To investigate the intraocular pressure (IOP) lowering effect of topical preserved tafluprost 0.0015% in a tertiary hospital setting in India.
METHODS
This is a retrospective chart review of patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) attending regular outpatient visits in December 2019 and January 2021, and treated with topical preserved tafluprost 0.0015%. Based on their medication history, patients were divided into two groups, the "treatment naïve" group and the "switched" group, which included patients switched to tafluprost monotherapy after treatment with at least one prior drug.
RESULTS
The mean IOP of the study population reduced significantly from baseline level by 20.6% and 25.5% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The mean IOP in patients with only OHT reduced significantly from baseline level by 21% and 26% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The mean IOP in patients with POAG reduced significantly from baseline level by 19% and 24% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The baseline IOP ± SD in POAG treatment naïve patients was 25.3 ± 0.3 mmHg, which reduced significantly by 24% and 28% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The baseline IOP ± SD in POAG switched patients was 24.3 ± 0.1 mmHg, which reduced significantly by 18% and 22% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). In the POAG switch group, the percent reduction in IOP at 3 months after preserved tafluprost 0.0015% treatment was 23% with timolol as first line, 22% with bimatoprost as first line, 20% with latanoprost as first line, and 19% with travoprost as first line (P < 0.001 for all).
CONCLUSIONS
We show significant IOP reduction with preserved tafluprost 0.0015% in a real-world setting. As first-line monotherapy in patients with OHT and in POAG-naïve patients, preserved tafluprost 0.0015% significantly reduced IOP at 3 months. Even as second-line therapy in nonresponders (POAG-Switched) to various drugs (same class [PGAs] versus different class), treatment with preserved tafluprost 0.0015% resulted in significant IOP reduction at 3 months.
Topics: Humans; Intraocular Pressure; Glaucoma, Open-Angle; Retrospective Studies; Prostaglandins F; Ocular Hypertension; Glaucoma; Timolol; Antihypertensive Agents; Treatment Outcome
PubMed: 37991299
DOI: 10.4103/IJO.IJO_3312_22 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Jun 2022Corpus luteum,an important endocrine tissue in mammalian ovary,plays a role in the regulation of reproductive cycle and the establishment of early pregnancy.While... (Review)
Review
Corpus luteum,an important endocrine tissue in mammalian ovary,plays a role in the regulation of reproductive cycle and the establishment of early pregnancy.While studying the luteal development and its molecular regulation,we have discovered a variety of immune cells,such as T lymphocytes,macrophages,neutrophils,and eosinophils,in the corpus luteum.These immune cells accumulate and support luteal angiogenesis and progesterone production during the luteal development,thus participating in the regulation of luteal functions.In luteal regression,prostaglandin F2 can stimulate the production of inflammatory cytokines and chemokines,which help immune cells enter the corpus luteum and enhance the decomposition of corpus luteum through inflammatory reactions.According to our research achievements,we reviewed the roles of different types of immune cells in the development and degradation of mammalian luteal functions,aiming to further understand the biology of corpus luteum and provide a reference for the clinical manipulation of luteal functions.
Topics: Animals; Corpus Luteum; Dinoprost; Female; Macrophages; Mammals; Ovary; Pregnancy; Progesterone
PubMed: 35791951
DOI: 10.3881/j.issn.1000-503X.13309 -
Biology of Reproduction May 2022In heifers and mares, multiple pulses of prostaglandin F2alpha (PGF) are generally associated with complete luteal regression. Although PGF pulses occur before and...
In heifers and mares, multiple pulses of prostaglandin F2alpha (PGF) are generally associated with complete luteal regression. Although PGF pulses occur before and during luteolysis, little is known about the role of minor PGF pulses during preluteolysis on subsequent luteal and endometrial PGF production that may initiate luteolysis. Heifers (n = 7/group) and mares (n = 6/group) were treated with a single minor dose of PGF (3.0 and 0.5 mg, respectively) during mid-luteal phase (12 and 10 days postovulation respectively). After treatment, a transient decrease in progesterone (P4) concentrations occurred in heifers between Hours 0 and 2 but at Hour 4 P4 was not different from pretreatment. In mares, P4 was unaltered between Hours 0 and 4. Concentrations of P4 decreased in both species by Hour 24 and complete luteolysis occurred in mares by Hour 48. Luteal and endometrial gene expression were evaluated 4 h posttreatment. In heifers, luteal mRNA abundance of PGF receptor and PGF dehydrogenase was decreased, while PTGS2, PGF transporter, and oxytocin receptor were increased. In the heifer endometrium, receptors for oxytocin, P4, and estradiol were upregulated. In mares, luteal expression of PGF receptor was decreased, while PGF transporter and oxytocin receptor were increased. The decrease in P4 between Hours 4 and 24 and changes in gene expression were consistent with upregulation of endogenous synthesis of PGF. The hypotheses were supported that a single minor PGF treatment upregulates endogenous machinery for PGF synthesis in heifers and mares stimulating endogenous PGF synthesis through distinct regulatory mechanisms in heifers and mares.
Topics: Animals; Cattle; Corpus Luteum; Dinoprost; Endometrium; Female; Horses; Luteolysis; Progesterone; Receptors, Oxytocin
PubMed: 35094051
DOI: 10.1093/biolre/ioac025 -
Respiratory Medicine 2021The purpose of this study was to investigate how 8-isoprostanes, used as a marker of airway oxidative stress, were related to sinus disease and asthma.
BACKGROUND
The purpose of this study was to investigate how 8-isoprostanes, used as a marker of airway oxidative stress, were related to sinus disease and asthma.
METHODS
We analyzed samples and data from two separate studies, one investigating sinonasal disease in asthma, the other investigating the effect of BMI on airway disease. We measured airway (nasal lavage) 8-isoprostanes and investigated the relationship with measures of sinus and asthma symptoms, asthma control and lung function.
RESULTS
The study of people with sinonasal disease and poorly controlled asthma included 48 obese, 31 overweight and 23 lean participants. In multivariate analysis, nasal lavage 8-isoprostane levels increased with increasing BMI (p < 0.01), and were higher in Caucasian than African American participants (p = 0.01). Sinus symptoms were inversely related to nasal 8-isoprostanes (p = 0.02) independent of BMI and Race. In the study investigating the effect of BMI on airway disease, we enrolled 13 controls with obesity and 21 people with obesity and asthma: 8-isoprostane levels were higher in obese controls than in obese people with asthma (p < 0.01), and levels were inversely related to sinus symptoms (p = 0.02) and asthma control (p < 0.01).
INTERPRETATION
8-isoprostanes in nasal lavage are increased in obesity, and increased in Caucasians compared with African Americans. However, levels are higher in obese controls than obese people with asthma, and appear inversely related to symptoms of airway disease.
CLINICAL IMPLICATION
Airway 8-isoprostanes likely reflect complex oxidative signaling pathways, which are altered in obesity and those of different race, rather than being a simple marker of airway oxidative injury.
CAPSULE SUMMARY
Increased airway oxidative signaling (8-isoprostanes), may reflect normal physiology in the setting of obesity, as decreased levels are associated with disease activity in people with chronic sinonasal disease and asthma.
Topics: Adult; Asthma; Biomarkers; Body Mass Index; Dinoprost; Female; Humans; Male; Middle Aged; Nasal Lavage Fluid; Obesity; Oxidative Stress; Paranasal Sinus Diseases; Racial Groups; Young Adult
PubMed: 34166960
DOI: 10.1016/j.rmed.2021.106506