PGE Concentrations Research Articles

In vitro study of carbetocin, an oxytocin receptor agonist, and 4-phenylfuroxan-3-carbonitrile, a NO-releasing agent, as cervical dilatators in sheep.

The aim was to study the effect of 4-phenylfuroxan-3-carbonitrile (Fx), a NO-releasing agent, and carbetocin, an oxytocin receptor agonist, on matrix metalloproteinases-2 (MMP-2) activity and PGE2 production in cervix from cycling sheep. Cervical explants were incubated during 12h with MEM supplemented with increasing concentrations of Fx in DMSO (2%) (0 to 300μg/mL) with Cb (100ng/mL) (Experiment 1, n=15) and DMSO (2%), DMSO+Cb (100ng/mL) or DMSO+Fx (30μg/mL) (Experiment 2, n=10), and their respective controls. In the supernatants, activated (A) and latent (L) MMP-2 activities were determined by a SDS-PAGE zymography, PGE2 concentration by immunoassay and NO production indirectly as nitrites by spectrophotometry. Data were analyzed by ANOVA. The Cb treatment increase the A MMP-2 activity in DMSO (Experiment 1 at follicular phase and Experiment 2) or alone (Experiment 2) and increase the L MMP-2 activity (Experiments 1 and 2) (P<0.02). The DMSO treatment also increase the L MMP2 activity (Experiment 2) (P<0.0001). Treatment with Fx+DMSO increased the concentration of accumulated nitrites in the supernatant (P<0.0001) (Experiment 1), but did not affect or decrease the activity of A and L MMP-2 (P<0.04) (Experiments 1 and 2). The PGE2 concentration trend to increase with Cb treatment (P=0.0614) and decrease with Fx+DMSO treatment (P<0.0001) (Experiment 2). In conclusion, Cb and/or DMSO treatment of cervical explants increase the MMP-2 activity through PGE2-independent mechanisms, but Fx in DMSO fail in this, suggesting that the pre-treatment with Cb and/or DMSO could be used to increase cervical dilation in ewes.

Prostaglandins Differentially Regulate the Constitutive and Mechanosensitive Release of Soluble Nucleotidases in the Urinary Bladder Mucosa.

The urothelium and lamina propria (LP) contribute to sensations of bladder fullness by releasing multiple mediators, including prostaglandins (PGs) and adenosine 5'-triphosphate (ATP), that activate or modulate functions of cells throughout the bladder wall. Mediators that are simultaneously released in response to bladder distention likely influence each other's mechanisms of release and action. This study investigated whether PGs could alter the extracellular hydrolysis of ATP by soluble nucleotidases (s-NTDs) released in the LP of nondistended or distended bladders. Using an ex vivo murine detrusor-free bladder model to access the LP during bladder filling and a sensitive HPLC-FLD detection methodology, we evaluated the decrease in ATP and the increase in adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP), and adenosine by s-NTDs released in the LP. Endogenous PGE2 increased the spontaneous but not the distention-induced release of s-NTD via EP2 and EP3 prostanoid receptors, whereas exogenous PGE2 increased the spontaneous s-NTD release via EP3, EP4, and FP receptors and the distention-induced s-NTD release via EP1-4 and FP receptors. Endogenous PGF2α, PGD2, and PGI2 did not change the s-NTD release. Exogenous PGD2 increased the spontaneous s-NTD release via DP2 receptors and the distention-induced s-NTD release via DP1 and DP2 receptors. Exogenous PGF2α increased the spontaneous but not the distention-induced release of s-NTD via FP receptors. It is possible that higher concentrations of PGE2, PGF2α, and PGD2 (as expected in inflammation, bladder pain syndrome, or overactive bladder) potentiate the release of s-NTDs and the consecutive degradation of ATP as a safeguard mechanism to prevent the development of excessive bladder excitability and overactivity by high amounts of extracellular ATP.

Investigation of Oxidative-Stress Impact on Human Osteoblasts During Orthodontic Tooth Movement Using an In Vitro Tension Model.

In recent years, there has been a growing number of adult orthodontic patients with periodontal disease. The progression of periodontal disease is well-linked to oxidative stress (OS). Nevertheless, the impact of OS on orthodontic tooth movement (OTM) is not fully clarified. Therefore, we applied an OS in vitro-model utilizing H2O2 to study its effect on tension-induced mechanotransduction in human osteoblasts (hOBs). Experimental parameters were established based on cell viability and proliferation. Apoptosis detection was based on caspase-3/7 activity. Gene expression related to bone-remodeling (RUNX2, P2RX7, TNFRSF11B/OPG), inflammation (CXCL8/IL8, IL6, PTRGS2/COX2), autophagy (MAP1LC3A/LC3, BECN1), and apoptosis (CASP3, CASP8) was analyzed by RT-qPCR. IL6 and PGE2 secretion were determined by ELISA. Tension increased the expression of PTRGS2/COX2 in all groups, especially after stimulation with higher H2O2 concentration. This corresponds also to the measured PGE2 concentrations. CXCL8/IL8 was upregulated in all groups. Cells subjected to tension alone showed a general upregulation of osteogenic differentiation-related genes; however, pre-stimulation with OS did not induce significant changes especially towards downregulation. MAP1LC3A/LC3, BECN1 and CASP8 were generally upregulated in cells without OS pre-stimulation. Our results suggest that OS might have considerable impacts on cellular behavior during OTM.

3. STUDY OF PROSTAGLANDIN E2 LEVEL IN PATIENTS WITH POLYPS AND COLORECTAL CANCER

Objectives: To describe the characteristics of age, sex; histopathology; some paraclinical features and to evaluate the concentration of Prostaglandin E2 in two groups of patients with polyps and colorectal cancer (CRC). Methods: Cross-sectional descriptive study on 308 patients: including 149 CRC patients and 109 patients with colorectal polyps diagnosed by cytology or histopathology, 50 healthy individuals; who were examined and treated at Military Hospital 175. Results: The mean age in the CRC group was 59,64 ± 11,66; in the colorectal polyps group was 58,45±9,65; in the healthy group was 57,32±8,17; there was no difference in age between the study groups. The incidence is higher in men than in women, and this difference is statistically significant (p=0,0061). Adenocarcinoma is dominant in CRC patients (77,85%); for polyps, adenomas are dominant (83,49%). The mean PGE2 concentration in CRC patients was 7,86±2,8 pg/ml; in polyp patients was 5,29±1,3 pg/ml; in healthy people it was 2,78±0,5 pg/ml. Conclusions: There was no difference in the concentration of PGE2 in the polyp and CRC groups (p&gt;0,05). However, there was a significant difference in PGE2 levels in the two groups of cancer and colorectal polyps compared to healthy individuals (p&lt; 0,05 (0,0021)).

Roles of Prostaglandins and Hydrogen Sulfide in an Outflow Model of the Porcine Ocular Anterior Segment Ex Vivo

Background: Hydrogen sulfide (H2S)-releasing compounds can reduce intraocular pressure in normotensive rabbits by increasing aqueous humor (AH) outflow through the trabecular meshwork. In the present study, we investigated the contribution of endogenous H2S and the role of intramurally generated prostaglandins in the observed increase in AH outflow facility in an ex vivo porcine ocular anterior segment model. Material and Methods: Porcine ocular anterior segment explants were perfused with Dulbecco’s Modified Eagle’s Medium maintained at 37 °C and gassed with 5% CO2 and 95% air under an elevated pressure of 15 mmHg for four hours. Perfusates from the anterior segment explants were collected and immediately assayed for their H2S and prostaglandin E2 content. Results: Elevating perfusion pressure from 7.35 to 15 mm Hg significantly (p &lt; 0.001) increased H2S concentration in the perfusate from 0.4 ± 0.1 to 67.6 ± 3.6 nM/µg protein. In the presence of an inhibitor of cystathionine ß-synthase/cystathionine γ-lyase, aminooxyacetic acid (AOAA, 30 µM), or an inhibitor of 3-mercaptopyruvate sulfurtransferase, α-ketobutyric acid (KBA, 1 mM), the effects of elevated pressure on H2S levels in the perfusate was significant (p &lt; 0.001). Furthermore, flurbiprofen (30 µM) and indomethacin (10 µM) attenuated the elevated pressure-induced increase in H2S levels in the perfusate. Interestingly, elevating perfusion pressure had no significant effect on PGE2 concentrations in the perfusate. While the inhibition of H2S biosynthesis by AOAA or KBA did not affect PGE2 levels in perfusate, flurbiprofen (30 µM) caused a significant (p &lt; 0.05) decrease in the concentration of PGE2 under conditions of elevated perfusion pressure. Conclusions: We conclude that the elevated perfusion pressure-induced increase in H2S concentrations depends upon the endogenous biosynthesis of H2S and intramurally produced prostaglandins in the porcine anterior segment explants. While the concentration of PGE2 in the perfusate under elevated perfusion pressure was unaffected by pretreatment with inhibitors of H2S biosynthesis, it was reduced in the presence of an inhibitor of cyclooxygenase.

The Effect of Mesenchymal Stem Cell Administration on the Expression of Nuclear Factor Kappa Beta, Neural Growth Factor Expression, and Prostaglandin E2 Concentration as Determinants of Pain in a Mouse Model of Endometriosis

Endometriosis is a significant reproductive health issue with pain being the primaru symptom. The complex pain in endometriosis involves the activation of macrophages, inflammatory activators such as NF-kB, neural growth factors (NGF), cytokines, adhesive molecules (ICAM-1), and mediators (PGE2) which they are stimulate sensory nerve fibers and produce nociceptive signals. This study is aim for investigate the effect of Mesenchymal Stem Cell (MSC) administration on the expression of NF-kB, NGF, and PGE2 concentration in a mouse model of endometriosis. Thirty-three mices were randomly divided into 3 groups consist non-endometriosis (P0), endometriosis without treatment (P1), and endometriosis with MSC administration (P2). The results showed MSC administration significantly reduced the expression of NF-kB by found scoring 2 groups (P1: 6.96 ± 0.13 and P2: 4.446 ± 0.228) and NGF (P1: 7.118 ± 0.629 and P2: 4.927 ± 1.187) also PGE2 (P1:1005.862 ± 176.656 and P2: 891.218 ± 54.031. In onclusion, this study demonstrates that MSC administration can able reduce the expression of NF-kB and NGF, but not to PGE2. The suggestion we can said is the MSC have potential therapeutic value in managing endometriosis-asssosciated pain by modulating inflammatory and neurotrophic factors. HIGHLIGHTS Pain in endometriosis, which is driven by inflammatory factors like NF-kB, NGF, cytokines, and PGE2, stimulating sensory nerve fibers and producing nociceptive signals. Investigate the effects of mesenchymal stem cell (MSC) administration on the expression of NF-kB, NGF, and PGE2 in a mouse model of endometriosis. Mesenchymal stem cell (MSC) administration was shown to reduce the expression of key inflammatory and neurotrophic factors—NF-kB and NGF—in a mouse model of endometriosis. Limited effect on reducing PGE2 concentration. These findings suggest that MSCs may have therapeutic potential for managing pain associated with endometriosis by modulating inflammatory and neurotrophic pathways. GRAPHICAL ABSTRACT

An advanced ultrasound-activated drug delivery system with piezocatalytic MoS2 nanoflowers for treating patent ductus arteriosus

Patent ductus arteriosus (PDA) is a prevalent cardiovascular anomaly that leads to considerable morbidity and mortality in premature infants. Although pharmacological interventions are commonly used for treatment, they often have notable adverse effects. This study introduces an innovative approach: a controlled drug delivery system that utilizes piezocatalyst nanocarriers produced through hydrothermal techniques. The synthesized nanoparticles undergo thorough characterization to assess their structural and morphological properties. Through ultrasound treatment, precise drug loading and efficient release of indomethacin (IDM) from chitosan (CS) stabilized molybdenum disulfide nanoflowers (MoS2-CS-IDM) are achieved. By harnessing ultrasound-induced reactive oxygen species, this method enables targeted drug delivery. Importantly, the nanoparticles demonstrate an approximately 60 % decrease in PGE2 concentrations, indicating their potential as anti-inflammatory agents. The favorable interaction of the nanoparticles with rat aortic smooth muscle cells and the successful closure of the ductus arteriosus in fetal Wistar rats validate their therapeutic effectiveness in vivo. In conclusion, the piezocatalyst-based drug delivery system presented in this study holds promise for versatile, biocompatible, and controlled drug release, with significant implications for therapeutic applications in PDA and potentially beyond.

Effects of radial extracorporeal shock wave with different frequencies on acute skeletal muscle injury in rabbits

To study the efficacy and possible mechanisms of radial extracorporeal shock wave (rESW) with different frequencies for the treatment of acute skeletal muscle injury in rabbits, 48 rabbits of acute injured biceps femoris were randomly divided into 4 groups. Except for the control group, the other groups were treated by rESW with 5 Hz, 10 Hz and 15 Hz, respectively. The injury symptom index scores (ISISs) in the rESW group were significantly lower than those in the control group, with the lowest in the 10 Hz rESW group. Histomorphological features demonstrated a decrease in mononuclear cells and an increase in new myocytes across all groups, with the rESW group showing the most significant changes. The concentrations of PGE2 and IL-1β were significantly lower in all rESW groups by ELISA compared to the control group. Additionally, the 10 Hz group had lower concentrations than the 5 Hz and 15 Hz group. Compared with the control group, MyoD of the rESW groups was significantly increased, and the expression level of the 10 Hz group was higher than that of the other groups. In conclusion, rESW with 5 Hz, 10 Hz and 15 Hz take certain curative effects on acute biceps femoris injury in rabbits, and the 10 Hz rESW takes advantage over 5 Hz and 15 Hz rESW.

Apatite and pyroxene as records of magmatic–hydrothermal processes and platinum-group mineral (PGM) formation in the Wengeqi mafic–ultramafic intrusion, Inner Mongolia, China: The role of oxidized, H2O-rich magmas

The Devonian Wengeqi mafic–ultramafic intrusion, situated on the northern margin of the North China Craton (NCC) — an Andean-style convergent margin during the Paleozoic — hosts many platinum-group minerals (PGMs), especially within the S-deficient, magnetite-rich clinopyroxenite zones. These PGMs occur in two distinct associations: Pt-rich PGMs (e.g., sperrylite) closely associated with primary magnetite and Pd-rich PGMs (e.g., sudburyite, kotuskite, arsenopalladinite) associated with secondary minerals (e.g., actinolite, pyrite). The mechanisms underlying the formation of PGMs in S-deficient rocks and the spatial decoupling of various PGM types remain elusive. The relationship of PGM formation and characteristics of magmas at convergent margins is also not well understood. In this contribution, we utilized apatite and clinopyroxene textures and chemistry alongside whole-rock SrNd isotopes to characterize i) the nature of the parental magma from which the Wengeqi intrusion crystallized, and ii) the magmatic–hydrothermal processes that operated to generate the Pt- and Pd-rich PGM. Based on the composition of clinopyroxene and clinopyroxene–melt partition coefficients, the parental magma of the Wengeqi intrusion is estimated to have an arc-like affinity on a primitive mantle-normalized trace-element diagram. This, together with the EMI-like SrNd isotope signature, implies that the Wengeqi magma was sourced from metasomatized SCLM beneath the NCC with an EMI-like composition. Three types of apatite (Ap1, Ap2, and Ap3) were identified within the intrusion. Ap1 and Ap2 are magmatic in origin, and appear as isolated grains, whereas Ap3 occurs as stringers or heterogeneous domains within Ap1 and Ap2, and likely resulted from hydrothermal modification of magmatic apatite. Notably, the abundant Ap2 exhibits higher VS contents and Eu/Eu* ratios than the less common Ap1, and contains S predominantly in the form of S6+, suggesting that the Wengeqi magma was relatively oxidized, with fO2 > FMQ + 1.2. Based on the chemistry of magmatic apatite, the Wengeqi magma had ∼5 wt% H2O, which, together with its high fO2, facilitated crystallization of magnetite, causing reduction of the magma by removal of Fe3+. This reduction process promoted PGM nucleation by decreasing PGE solubility in the magma, leading to the association of PGM with magnetite. Additionally, the oxidized, H2O-rich magma likely released oxidizing fluids, selectively mobilizing Pd rather than Pt, separating Pt-rich PGMs from Pd-rich PGMs. The budget of PGE in the parental magma could have been increased by i) metasomatism of the SCLM source (e.g., by carbonatitic fluids), which would have elevated the concentration of PGE in the mantle source, and ii) the high fO2 and H2O levels of the magma, which would have delayed sulfide saturation. Accordingly, mantle metasomatism and high fO2–H2O are deemed favorable for enrichment of PGE in magmas within convergent margins.

Effects of using different biological products on IL-1β TNF-α, PGE2 concentrations in rabbits with periodontitis

Effects of using different biological products on IL-1β TNF-α, PGE2 concentrations in rabbits with periodontitis

Longitudinal in vivo cationic contrast-enhanced computed tomography classifies equine articular cartilage injury and repair.

Cationic contrast-enhanced computed tomography (CECT) capitalizes on increased contrast agent affinity to the charged proteoglycans in articular cartilage matrix to provide quantitative assessment of proteoglycan content with enhanced images. While high resolution microCT has demonstrated success, we investigate cationic CECT use in longitudinal in vivo imaging at clinical resolution. We hypothesize that repeated administration of CA4+ will have no adverse side effects or complications, and that sequential in vivo imaging assessments will distinguish articular cartilage repair tissue from early degenerative and healthy cartilage in critically sized chondral defects. In an established equine translational preclinical model, lameness and synovial effusion scores are similar to controls after repeated injections of CA4+ (eight injections over 16 weeks) compared to controls. Synovial fluid total protein, leukocyte concentration, and sGAG and PGE2 concentrations and articular cartilage and synovial membrane scores are also equivalent to controls. Longitudinal in vivo cationic CECT attenuation in repair tissue is significantly lower than peripheral to (adjacent) and distantly from defects (remote sites) by 4 weeks (p < 0.001), and this difference persists until 16 weeks. At the 6- and 8-week time points, the adjacent locations exhibit significantly lower cationic CECT attenuation compared with the remote sites, reflecting peri-defect degeneration (p < 0.01). Cationic CECT attenuation at clinical resolution significantly correlates with cationic CECT (microCT) (r = 0.69, p < 0.0001), sGAG (r = 0.48, p < 0.0001), and ICRS II histology score (r = 0.63, p < 0.0001). In vivo cationic CECT imaging at clinical resolution distinguishes fibrous repair tissue from degenerative and healthy hyaline cartilage and correlates with molecular tissue properties of articular cartilage.

The Effect of Intracameral Triamcinolone Acetonide on Controlling Common Complications following Phacoemulsification in Dogs.

The intracameral injection of triamcinolone acetonide (TA) has achieved favorable clinical effects in controlling intraocular inflammatory reactions in humans after cataract surgery. However, the effect of this method remains unclear in veterinary practice. In this paper, 18 dogs with bilateral cataracts were randomly divided into three groups, with 6 dogs in each group. Phacoemulsification and intraocular lens implantation were performed on the 36 eyes of these dogs. A total of 0.1 mL of TA solution was injected into the oculus dexter (OD) anterior chambers. All oculus sinister (OS) anterior chambers of these dogs were used as controls. The results demonstrated that the corneal edema severity scores of the OD (1.5 mg TA) were lower than those of the OS from the 1st to 7th day after surgery, with a significant difference on the 3rd day after surgery (p = 0.033). The corneal edema severity scores in the OD (1.5 mg TA) were significantly lower than those in the OD (0.5 mg TA) on the 3rd day after surgery (p = 0.036). The aqueous humor protein concentration of the OD (1.5 mg TA) had a lower concentration than the OS on the 1st day after surgery (p = 0.004). Furthermore, on the 5th and 10th days, the aqueous humor protein concentration of the OD (1.5 mg TA) was lower than that of the OS (p = 0.038 and p = 0.044, respectively). The aqueous humor PGE2 concentration of the OD (1.5 mg TA) had a lower concentration than the OS on the 1st day after surgery (p = 0.026). The aqueous humor PGE2 concentrations in the OD (1.0 mg TA) and OD (1.5 mg TA) were lower compared to that in the OD (0.5 mg TA) on the 1st day after surgery (p = 0.041 and p = 0.037, respectively). It was demonstrated that TA-based treatment can be safely employed to effectively control common complications after phacoemulsification in dogs.

Intrauterine devices influence prostaglandin secretion by equine uterus: in vitro and in vivo studies

BackgroundIntrauterine devices (IUD) are used in the veterinary practice as the non-pharmacological method of oestrus suppression in mares. When placed in the uterus, IUD create a physical contact with the endometrium that mimics the presence of an equine embryo. However, the mechanism of their action has not been fully elucidated. The objective of the present study was to examine the effect of mechanical stimulation of IUD on mare`s endometrium in both in vitro and in vivo study. For this purpose, we demonstrated the effect of IUD on prostaglandin (PG) F2α and PGE2 secretion, and mRNA transcription of genes involved in PG synthesis pathway in equine endometrial cells in vitro. In the in vivo study, we aimed to compare short-term effect of IUD inserted on day 0 (oestrus) with day 5–6 post-ovulation (the specific time when embryo reaches uterus after fertilization) on PG secretion from equine endometrium. To determine the long-term effect on PG synthase mRNA transcription, a single endometrial biopsy was taken only once within each group of mares at certain time points of the estrous cycle from mares placement with IUD on days 0 or 5–6 post-ovualtion.ResultsWe showed for the first time that the incubation of the endometrial cells with the presence of IUD altered the pattern of PG synthase mRNA transcription in equine epithelial and stromal endometrial cells. In vivo, in mares placement with IUD on day 0, PGE2 concentrations in blood plasma were upregulated between 1 and 6, and at 10 h after the IUD insertion, compared with the control mares (P < 0.05). Moreover, the decrease of PTGFS mRNA transcription on day 16- 18, associated with an elevation in PTGES mRNA transcription on day 20 -21 of the estrous cycle in endometrial biopsies collected from mares placement with IUD on days 5–6 suggest an antiluteolytic action of IUD during the estrous cycle.ConclusionWe conclude that the application of IUD may mimic the equine conceptus presence through the physical contact with the endometrium altering PG synthase transcription, and act as a potent modulator of endometrial PG secretion both in vitro and in vivo.

Antipyretic effects of Xiangqin Jiere granules on febrile young rats revealed by combining pharmacodynamics, metabolomics, network pharmacology, molecular biology experiments and molecular docking strategies

Xiangqin Jiere granules (XQJRG) is a proprietary Chinese medicine treating children’s colds and fevers, but its mechanism of action is unclear. The aim of this study was to explore the antipyretic mechanisms of XQJRG based on pharmacodynamics, non-targeted metabolomics, network pharmacology, molecular biology experiments, molecular docking, and molecular dynamics (MD) simulation. Firstly, the yeast-induced fever model was constructed in young rats to study antipyretic effect of XQJRG. Metabolomics and network pharmacology studies were performed to identify the key compounds, targets and pathways involved in the antipyretic of XQJRG. Subsequently, MetScape was used to jointly analyze targets from network pharmacology and metabolites from metabolomics. Finally, the key targets were validated by enzyme-linked immunosorbent assay (ELISA), and the affinity and stability of key ingredient and targets were evaluated by molecular docking and MD simulation. The animal experimental results showed that after XQJRG treatment, body temperature of febrile rats was significantly reduced, 13 metabolites were significantly modulated, and pathways of differential metabolite enrichment were mainly related to amino acid and lipid metabolism. Network pharmacology results indicated that quercetin and kaempferol were the key active components of XQJRG, TNF, AKT1, IL6, IL1B and PTGS2 were core targets. ELISA confirmed that XQJRG significantly reduced the plasma concentrations of IL-1β, IL-6, and TNF-α, and the hypothalamic concentrations of COX-2 and PGE2. Molecular docking demonstrated that the binding energies of kaempferol to the core targets were all below −5.0 kcal/mol. MD simulation results showed that the binding free energies of TNF-kaempferol, IL6-kaempferol, IL1B-kaempferol and PTGS2-kaempferol were −87.86 kcal/mol, −70.41 kcal/mol, −69.95 kcal/mol and −106.67 kcal/mol, respectively. In conclusion, XQJRG has antipyretic effects on yeast-induced fever in young rats, and its antipyretic mechanisms may be related to the inhibition of peripheral pyrogenic cytokines release by constituents such as kaempferol, the reduction of hypothalamic fever mediator production, and the amelioration of disturbances in amino acid and lipid metabolism. Communicated by Ramaswamy H. Sarma

Effects of forskolin and PGE2 on progesterone secretion by goat luteal cells at early and late stages of corpus luteum

The aim of this research was to examine the effects of forskolin and PGE2 on steroid synthesis in goat luteal cells, cultured at early and late corpus luteum. Therefore, the luteal cells removed from both stages of the corpus luteum were cultured with newborn calf serum for the first 18 h. Then the media was changed and different concentrations of forskolin (10, 100 ng/ml) or PGE2 (10, 100 ng/ml) were added to the fresh media for another 96 h. The culture media was replaced every 48 h and the retrieval media was kept frozen at -20 °C, until hormone analysis. Luteal cells treated with forskolin produced between 1.87-13.17 times higher production of progesterone, in a dose-dependent manner, compared to the control at early and late stages of corpus luteum (P&amp;lt;0.05). Lower dose of PGE2 increased the progesterone secretion between 2.19-3.28 times in luteal cells compared to the control groups at the late stage of corpus luteum (P&amp;lt;0.05), but not at early stage. The cells treated with a higher dose of PGE2 had no significant effect (P&amp;gt;0.05) on progesterone synthesis at the early and late phases of goat corpus luteum, in comparison to control groups. As a result, this study in goat luteal cells shows that forskolin promotes progesterone synthesis at the early and late corpus luteum, but PGE2 is only effective in cells treated with a low dose at the late stage.

Conditioned medium of IGF-1-induced human synovial membrane mesenchymal stem cells effects on inflammatory response of osteoarthritic in vitro model

Synovial membrane mesenchymal stem cells (SM-MSCs) possess excellent regenerative potential, making them a viable option for osteoarthritis (OA) therapy. Moreover, these cells can be easily obtained from the human body. Insulin-like growth factor (IGF-1) can be used to decrease the pro-inflammatory marker, these markers can trigger inflammation in OA. These challenges can be addressed by utilizing a conditioned medium (CM) derived from stem cell culture. This study aims to compare the effective way of OA therapy between CM SM-MSC and CM SM-MSC induced by IGF-1 by observe the pro-inflammatory markers such as NF-kB, RANTES, PGE2, COL1 and the anti-inflammatory marker, Aggrecan (ACAN). Chondrocyte cells induced IL-1β as OA model (IL1β-CHON002) treated with IGF-1 15% and 30% and without IGF1-induced SM-MSCs-CM to know its effectiveness in decreasing the pro-inflammatory markers. ELISA and RT-qPCR methods were performed to analyze this effect. Based on the data result, SM-MSCs-CM is estimated to have the potential to treat OA as seen from the content of growth factors in CM, decreasing the markers of inflammation. The most significant reduction in PGE2, RANTES, NF-kB, and COL1 concentration was found in the treatment of SM-MSCs-CM cultured with IGF1 concentrations of 150 ng/mL. The higher aggrecan (ACAN) concentration was found in IGF150 15%. Conclusion: CM from SM-MSCs cultured with IGF150 with concentrations of 15% and 30% resulted in the most effective concentration to decrease the concentration of pro-inflammatory markers and also to increase the anti-inflammatory markers.

Influences of subduction derived fluids and melt in the genesis of Nidar ophiolite peridotites, Ladakh Himalaya, India: Evidence from mineralogy, PGE and Nd isotopic compositions

The Nidar ophiolite is one of the well-preserved and almost complete ophiolite sections of the Neo-Tethyan oceanic lithosphere, obducted along the continental margin between the Indian and the Eurasian plate. This ophiolite sequence is mostly dominated by ultramafic rocks, consisting of forearc-related refractory, mainly harzburgite, dunite, and serpentinite, with minor intrusions of lherzolite, chromitites, and pyroxenites. In this present study, detailed mineralogical, whole rock geochemistry (major oxides, trace elements, PGE), and Nd isotopic composition of mantle-derived peridotites have been carried out to constrain the petrogenesis and melt evolution. These peridotites are depleted in nature due to the low modal composition of clinopyroxene, high forsterite content in olivine, and wide variation in Cr# and bulk rock chemistry, indicating variable degree of partial melting. The spoon-shaped rare earth element (REE) patterns indicate metasomatism by fluids derived from a subducting slab enriched in light REEs. Geochemical composition of the studied peridotites rocks is marked by high ratio of Al2O3/TiO2, LILE-LREE enrichment, HFSE depletion, and spoon-shaped chondrite-normalized REE patterns and (La/Sm)N > 1 and (Gd/Yb)N < 1, indicates some involvement of boninitic mantle melts and validate a subduction initiation process. The total PGE of the peridotites (ΣPGE = 33–337 ppb) is much more enriched than that of the primitive mantle and other ophiolite peridotites. The PGE distribution displays a concave upward pattern with higher PPGE/IPGE ratios (i.e., 0.11–1.45), suggesting that partial melting is not the only process for the evolution of the Nidar ophiolite peridotites. Enrichment of PPGE and incompatible elements (like LREE) and higher Pd/Ir ratio (0.69–8.26) indicates that these peridotites have undergone fluid/melt interaction in a supra-subduction zone (SSZ) tectonic setting. PGE concentrations of these depleted harzburgites and dunites, formed by partial melting of cpx–harzburgites in an SSZ that produced the boninitic-like melt. The enrichment of incompatible elements like the PPGE is mainly due to the circulation of fluids in the subduction zone, which leads to the PGE fractionation in mantle peridotites. Also, these peridotites have 143Nd/144Nd ratios (0.51148–0.51262) and εNd(t) (t = 140 Ma) values (i.e., +0.97 to −21.3), indicating derivation from depleted mantle sources within an intra-oceanic arc setting. The geochemical behavior exhibited by the Nidar ophiolite peridotites suggests the evolution of a highly depleted fore-arc mantle wedge significantly modified by various fluids and melts during subduction. The mineralogical, geochemical, and Nd isotopic composition of these peridotites and dunites mutually depict the diverse mantle compositions, suggesting insights into the interactions between the oceanic crust and mantle as well as associated geochemical cycling in an SSZ environment.

Hydrogen Sulfide-Releasing Indomethacin-Derivative (ATB-344) Prevents the Development of Oxidative Gastric Mucosal Injuries.

Hydrogen sulfide (H2S) emerged recently as an anti-oxidative signaling molecule that contributes to gastrointestinal (GI) mucosal defense and repair. Indomethacin belongs to the class of non-steroidal anti-inflammatory drugs (NSAIDs) and is used as an effective intervention in the treatment of gout- or osteoarthritis-related inflammation. However, its clinical use is strongly limited since indomethacin inhibits gastric mucosal prostaglandin (PG) biosynthesis, predisposing to or even inducing ulcerogenesis. The H2S moiety was shown to decrease the GI toxicity of some NSAIDs. However, the GI safety and anti-oxidative effect of a novel H2S-releasing indomethacin derivative (ATB-344) remain unexplored. Thus, we aimed here to compare the impact of ATB-344 and classic indomethacin on gastric mucosal integrity and their ability to counteract the development of oxidative gastric mucosal injuries. Wistar rats were pretreated intragastrically (i.g.) with vehicle, ATB-344 (7-28 mg/kg i.g.), or indomethacin (5-20 mg/kg i.g.). Next, animals were exposed to microsurgical gastric ischemia-reperfusion (I/R). Gastric damage was assessed micro- and macroscopically. The volatile H2S level was assessed in the gastric mucosa using the modified methylene blue method. Serum and gastric mucosal PGE2 and 8-hydroxyguanozine (8-OHG) concentrations were evaluated by ELISA. Molecular alterations for gastric mucosal barrier-specific targets such as cyclooxygenase-1 (COX)-1, COX-2, heme oxygenase-1 (HMOX)-1, HMOX-2, superoxide dismutase-1 (SOD)-1, SOD-2, hypoxia inducible factor (HIF)-1α, xanthine oxidase (XDH), suppressor of cytokine signaling 3 (SOCS3), CCAAT enhancer binding protein (C/EBP), annexin A1 (ANXA1), interleukin 1 beta (IL-1β), interleukin 1 receptor type I (IL-1R1), interleukin 1 receptor type II (IL-1R2), inducible nitric oxide synthase (iNOS), tumor necrosis factor receptor 2 (TNFR2), or H2S-producing enzymes, cystathionine γ-lyase (CTH), cystathionine β-synthase (CBS), or 3-mercaptopyruvate sulfur transferase (MPST), were assessed at the mRNA level by real-time PCR. ATB-344 (7 mg/kg i.g.) reduced the area of gastric I/R injuries in contrast to an equimolar dose of indomethacin. ATB-344 increased gastric H2S production, did not affect gastric mucosal PGE2 content, prevented RNA oxidation, and maintained or enhanced the expression of oxidation-sensitive HMOX-1 and SOD-2 in line with decreased IL-1β and XDH. We conclude that due to the H2S-releasing ability, i.g., treatment with ATB-344 not only exerts dose-dependent GI safety but even enhances gastric mucosal barrier capacity to counteract acute oxidative injury development when applied at a low dose of 7 mg/kg, in contrast to classic indomethacin. ATB-344 (7 mg/kg) inhibited COX activity on a systemic level but did not affect cytoprotective PGE2 content in the gastric mucosa and, as a result, evoked gastroprotection against oxidative damage.

Hibiscus syriacus L. Extract by ultrasonic assistance displays anti-inflammatory and pro-apoptotic activity in LPS-stimulated Raw 264.7 cells

Hibiscus syriacus L. extract (HSE) traditionally has been recognized as promising natural resources for the treatment of diseases related to hyper-inflammation. This study aimed to investigate the anti-inflammatory effect of HSE in LPS-stimulated Raw 264.7 cells. For this purpose, we determined the optimal extraction method and found that the ultrasonic extraction showed the most effective activity for reduction of free radical species by DPPH assay. Then, we performed PGE2 concentration analysis, COX-2 activity assay, proliferation assay, apoptosis detection, and western blotting analysis. HSE decreased PGE2 concentration and COX-2 activity and reduced the expression of COX-2 and IL6 in LPS stimulated Raw 264.7 cells. In addition, we found that HSE inhibited the proliferation and induced apoptosis with increase in the expression of pro-apoptotic proteins such as caspase-3, -7, -9, Bax, Bim, FOXO3, and p53 in LPS-stimulated Raw 264.7 cells. Taken together, we found that HSE effectively suppressed LPS-stimulated Raw 264.7 cells suggesting that HSE has the potential to treat inflammation via regulation of proinflammatory COX-2, IL6, and PGE2 and induction of apoptosis.

Expression of steroidogenic enzymes in placentome of ewes with pregnancy toxemia after two parturition induction methods

The regulation pattern of important enzymes in placental steroidogenesis and prostaglandins in ewes with pregnancy toxemia is reviewed. The alterations of gene expressions after the administration of aglepristone and dexamethasone are also discussed. Four healthy and 22 ewes with pregnancy toxemia were included to the study. Group AG (n=9) and Group DEX (n=9) in which ewes were injected twice with 10 mg/kg of aglepristone and once with 5 ml dexamethasone, respectively; whereas negative control [Group CG (n=4)] and pregnancy toxemia [Group PT (n=4)] groups received no treatment for parturition induction. Placentomes were collected either right after parturition or C-section. mRNA extraction from total placentome, caruncle, cotyledon and caruncle part of placentomes was carried out and Real-Time PCR was performed. Serum samples were collected and cortisol, PGFM, PGE2 and estrone sulfate concentrations were measured after treatments until parturition. The lowest mRNA expressions of steroidogenic enzymes were detected in group PT. Interestingly similar expression pattern of steroidogenic enzymes in group AG was as similar as group PT. No difference was found in expressions of 3βHSD and CYP19. PTGS2/COX2 and PGFS mRNA expressions were statistically different between groups AG-DEX and in caruncle between groups, respectively (P&lt;0.005). Significant difference could clearly be observed in EP3 expression in caruncle of DEX and AG compared to CG (P&lt;0.005); however PTGES, EP1, EP2 and EP4 expressions were not statistically different among groups (P&gt;0,05). Ostrone sulfate, PGE2 and PGFM concentrations were statistically different according to the sampling time between groups however no difference was observed in cortisol. The present study has suggests that the endocrinologic pathway controlling parturition is clearly different in ewes with pregnancy toxemia. Spontaneous parturition could occur as a consequence of immune and inflammatory processes, which could be activated by by-products of fat metabolism. Dexamethasone applications has mimicked normal parturition, however the gene expression regulations, controlling uterine contractions, are observed as similar as group PT. Probably expressions of EP1 and tissue-specific counter-expressions of cervical EP genes could refer the pathogenesis of insufficient cervical dilatation, observed in pregnancy toxemia and dexamethsone applications.