PGF2α Concentrations Research Articles

Multi-Omics Reveals the Role of Arachidonic Acid Metabolism in the Gut-Follicle Axis for the Antral Follicular Development of Holstein Cows.

In vitro embryonic technology is crucial for improving farm animal reproduction but is hampered by the poor quality of oocytes and insufficient development potential. This study investigated the relationships among changes in the gut microbiota and metabolism, serum features, and the follicular fluid metabolome atlas. Correlation network maps were constructed to reveal how the metabolites affect follicular development by regulating gene expression in granulosa cells. The superovulation synchronization results showed that the number of follicle diameters from 4 to 8 mm, qualified oocyte number, cleavage, and blastocyst rates were improved in the dairy heifers (DH) compared with the non-lactating multiparous dairy cows (NDC) groups. The gut microbiota was decreased in Rikenellaceae_RC9_gut_group, Alistipes, and Bifidobacterium, but increased in Firmicutes, Cyanobacteria, Fibrobacterota, Desulfobacterota, and Verrucomicrobiota in the NDC group, which was highly associated with phospholipid-related metabolites of gut microbiota and serum. Metabolomic profiling of the gut microbiota, serum, and follicular fluid further demonstrated that the co-metabolites were phosphocholine and linoleic acid. Moreover, the expression of genes related to arachidonic acid metabolism in granulosa cells was significantly correlated with phosphocholine and linoleic acid. The results in granulosa cells showed that the levels of PLCB1 and COX2, participating in arachidonic acid metabolism, were increased in the DH group, which improved the concentrations of PGD2 and PGF2α in the follicular fluid. Finally, the expression levels of apoptosis-related proteins, cytokines, and steroidogenesis-related genes in granulosa cells and the concentrations of steroid hormones in follicular fluid were determinants of follicular development. According to our results, gut microbiota-related phosphocholine and linoleic acid participate in arachidonic acid metabolism in granulosa cells through the gut-follicle axis, which regulates follicular development. These findings hold promise for enhancing follicular development and optimizing oocyte quality in subfertile dairy cows.

Insights into the role of PGF2α in canine periparturient myometrium.

Parturition in dogs is subjected to complex hormonal regulation, with the involvement of prostaglandin F2α (PGF2α) still not fully understood. To investigate uterine inertia (UI), the most prevalent maternal reason for dystocia in the bitch, a better understanding of undisturbed uterine, especially myometrial function, is crucial. Our aim was to gain deeper insights into the role of PGF2α in the canine parturient myometrium. Uterine biopsies were obtained during medically indicated cesarean sections. To test for stimulatory effects of PGF2α in vitro, circular and longitudinal myometrial layer tissue strips were challenged with 50pM, 0.5µM, and 50µM PGF2α. Prostaglandin-endoperoxide synthase 2 (PTGS2) and PGF2α-receptor (PTGFR) mRNA expressions were compared between primary UI (PUI) and obstructive dystocia (OD) samples in isolated parturient myometrium. PTGFR protein expression was assessed in full thickness uterine samples. PGF2α concentrations were analyzed in canine interplacental tissue around term. In the organ bath, the contractile response to PGF2α was limited to the circular layer at the highest dosage. Correspondingly, PTGFR immunohistochemical staining was significantly stronger in the circular layer (p ≤ 0.01). PTGS2 gene expression did not differ between PUI and OD, whereas PTGFR gene expression could not be quantified. Local uterine PGF2α concentrations correlated negatively with serum P4 levels and were the highest during prepartum luteolysis while being significantly lower in PUI. Conclusively, despite the significant increase in local PGF2α concentrations at birth, confirming the interplacental tissue as a production site, our results suggest that PGF2α might affect uterine contractility during labor, mainly indirectly.

The Essential Role of PGF2α/PTGFR in Molding Endometrial Breakdown and Vascular Dynamics, Regulated by HIF-1α in a Mouse Menstrual-like Model.

In women of childbearing age, extensive decidualization, shedding and remodeling of the endometrium during the menstrual cycle are fundamental for successful pregnancy. The role of prostaglandins (PGs) in menstruation has long been proposed in humans, and the rate-limiting enzyme cyclooxygenase was shown to play a key role in endometrial breakdown and shedding in a mouse menstrual-like model in our previous study. However, the specific types of PGs involved and their respective roles remain unclear. Therefore, our objective was to investigate the mechanism through which PGs regulate endometrial disintegration. In this study, the microscopy was observed by HE; the protein levels of prostaglandins E1 (PGE1), prostaglandins E2 (PGE2), prostaglandin F2α (PGF2α) and Prostaglandin I2 (PGI2) were detected by ELISA; the mRNA level of Pfgfr2, Vascular Endothelial Growth Factor(Vegf), Angiostatin and Hypoxia inducible factor-1α (Hif1α) were examined by real-time PCR; PTGFR Receptor (PTGFR), VEGF, Angiostatin and HIF-1α protein levels were investigated by western blotting; the locations of protein were observed by Immunohistochemistry; HIF-1α binding PTGFR promoter was detected by Chromatin Immunoprecipitation (ChIP) and real-time PCR. We found that the concentrations of PGE1, PGE2, and PGF2α all increased significantly during this process. Furthermore, Ptgfr mRNA increased soon after Progesterone (P4) withdrawal, and PTGFR protein levels increased significantly during abundant endometrial breakdown and shedding processes. PTGFR inhibitors AL8810 significantly suppressed endometrial breakdown and shedding, promoted Angiostatin expression, and reduced VEGF-A expressions and vascular permeability. And HIF-1α and PTGFR were mainly located in the luminal/gland epithelium, vascular endothelium, and pre-decidual zone. Interestingly, HIF-1α directly bound to Ptgfr promoter. Moreover, a HIF-1α inhibitor 2-methoxyestradiol (2ME) significantly reduced PTGFR expression and suppressed endometrial breakdown which was in accord with PTGFR inhibitor's effect. Similar changes occurred in human stromal cells relevant to menstruation in vitro. Our study provides evidence that PGF2α/PTGFR plays a vital role in endometrial breakdown via vascular changes that are regulated by HIF-1α during menstruation.

Study on the mechanism of Panax notoginseng-Salvia miltiorrhiza herb pair on invigorating blood circulation and eliminating blood stasis by blocking the conversion of arachidonic acid to prostaglandin.

We combined untargeted and targeted metabolomics to explore the mechanism of blood circulation and blood stasis activation in the traditional Chinese herb pair Panax notoginseng-Salvia miltiorrhiza (PS). In this study, the right hind limb of SD rats was struck by a 1kg weight, causing traumatic blood stasis (TBS) model, then the rats were gavaged with PS (at ratios of 1:0, 0:1, 3:1, 1:1, and 1:3) for 5 consecutive days. At the end of treatment, blood samples were collected for blood rheology and metabolomics analysis, and muscle tissues of injured limbs were used for HE staining and q-PCR analysis. The results showed that different ratios of PS reduced swelling and improved stasis and blood viscosity in the injured limbs of rats, and intervened in metabolism by modulating 11, 11, 17, 15, and 13 differential metabolites, respectively. The PS (3:1) shows the best treatment effect and the most differential metabolites regression. Targeted metabolomics shows that PS (3:1) can increase the content of AA, and reduce the content of PGF2-α by down-regulating the expression of enzymes Ptgs1 and Cbrl12 and up-regulating the expression of enzyme Hpgd. These results suggested that the PS herb pair exerts its blood stasis activating effects by blocking the conversion of arachidonic acid to prostaglandins.

Effects of firocoxib, trimethoprim sulfamethoxazole and altrenogest on inflammation and foal survival after administration to mares with experimentally induced placentitis

Bacterial placentitis is a leading cause of pregnancy loss in mares. Infection, inflammation and prostaglandin production induce preterm delivery leading to poor foal survival. Treatment strategies for placentitis that control infection and inhibit inflammation are vital. The goals of this study were: 1. Assess the anti-inflammatory effects of firocoxib, trimethoprim sulfamethoxazole (TMS) and altrenogest administered to mares with placentitis; 2. Determine the efficacy of firocoxib, TMS and altrenogest for improving foal outcome in mares with placentitis. We hypothesized that this treatment would significantly decrease pro-inflammatory mediators in fetal fluids and tissues when compared to untreated, infected mares and would also improve foal survival. Placentitis was induced in 13 pregnant mares (270-300 days gestation; via intracervical inoculum of Streptococcus zooepidemicus). Mares were randomly assigned to: infected/untreated (UNTREATED; n=6); or infected/treated groups (TREATED; n=7; administered firocoxib, TMS, and altrenogest from the onset of clinical signs of placentitis until abortion/delivery). Fetal fluids, membranes and tissue samples were obtained at abortion/delivery for quantification of TNF-α, IL-1β, IL-10, IL-6, IL-8, PGE2, PGF2α, and matrix metalloproteinases (MMP) -1, -3, -9 using ELISA (fluids) and real-time PCR (tissues). P < 0.05 was considered significant. Gestation length and foal survival were significantly higher in TREATED (mean days post-infection = 40; 7/7 live foals) than UNTREATED (mean days post-infection = 14; 2/6 live foals). Administration of firocoxib, TMS andaltrenogest resulted in significantly lower amniotic fluid concentrations of IL-1β, IL-6, PGE2 and PGF2α in TREATED than UNTREATED. Amniotic fluid IL-10 concentration tended (P < 0.1) to be lower in TREATED than UNTREATED. Cytokine and prostaglandin concentrations in allantoic fluid were not different between groups except PGE2 which tended (P < 0.1) to be lower in TREATED than UNTREATED. The relative quantity of cytokine and MMP mRNA expression in fetal membranes and foal tissues (non-survivors) was log-transformed and estimated marginal means determined. Fetal membranes from TREATED had significantly lower mRNA expression for IL-8 and TNFα compared to membranes from UNTREATED. mRNA expression of IL-1β, IL-6 and MMP3 tended (P < 0.1) to be lower in membranes from TREATED than UNTREATED. mRNA expression of IL-1β, IL-8, IL-10, TNFα, MMP1, 3 and 9 were significantly different between fetal membrane sites. In non-surviving foals, IL-8 mRNA expression was significantly lower in liver than lung while MMP3 expression was significantly higher in liver than lung or spleen. These data provide physiologic evidence that administration of firocoxib, TMS and altrenogest to mares with placentitis has broad anti-inflammatory effects and may improve foal survival. Research funding: Grayson Jockey Club Research Foundation; Merial Animal Health; Kentucky Thoroughbred Breeders Association, University of Florida, University of Georgia.

An IFNT/FOXO1/PTGS2 axis regulates prostaglandin F2α synthesis in goat uterus during early pregnancy

In ruminants, interferon tau (IFNT) regulates the production of prostaglandins (PGs) in the endometrium, which is crucial for conceptus adhesion. However, the related molecular regulatory mechanisms remain unclear. Forkhead box O1 (FOXO1), a member of the FOXO subfamily of transcription factors, is known to be important for mouse implantation and decidualization. In this study, we determined the spatiotemporal expression profile of FOXO1 in goat endometrium during early pregnancy. FOXO1 was highly expressed in the glandular epithelium (GE) since the onset of conceptus adhesion (d 16 of pregnancy). Then, we validated that FOXO1 could bind to the promoter of prostaglandin-endoperoxide synthase 2 (PTGS2) and increase its transcription. And the expression profile of PTGS2 was similar to that of FOXO1 in the peri-implantation uterus. Moreover, IFNT could upregulate the levels of FOXO1 and PTGS2 in goat uterus and primary endometrial epithelium cells (EECs). In EECs, the intracellular content of PGF2α was positively correlated with the levels of IFNT and FOXO1. Altogether, we found an IFNT/FOXO1/PTGS2 axis that controls the synthesis of PGF2α but not PGE2 in goat uterine glands. These findings contribute to better understanding the function of FOXO1 in the reproductive physiology of goats and provide more insights into the implantation of small ruminants.

Effects of electroacupuncture on N-methyl-D-aspartate receptor and mitogen activated protein kinase in spinal cord of rats with primary dysmenorrhea

To observe the effects of electroacupuncture (EA) on the expression levels of N-methyl-D-aspartate receptor (NMDAR), extracellular signal-regulated kinase (ERK)1/2, p38 mitogen activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) in the spinal cord of rats with primary dysmenoramia (PDM), so as to explore the underlying mechanism of EA treating PDM. Thirty female SD rats were randomly divided into normal group, model group and EA group, with 10 rats in each group. The PDM rat model was established by subcutaneous injection of estradiol benzoate and oxytocin into the thigh. At the same time of modeling, rats in the EA group were treated with EA (50 Hz) at "Sanyinjiao" (SP36) and "Guanyuan" (CV4) once daily, 20 min each time, for 10 consecutive days. The writhing times, writhing score and writhing latency were observed within 30 min after oxytocin injection. The uterine pathological morphology was observed by HE staining, and pathological score was calculated. Serum prostaglandin F2α (PGF2α) and prostaglandin E2 (PGE2) were determined by ELISA. The protein expression levels of NMDAR, ERK1/2, p38MAPK and JNK in spinal cord were detected by Western blot. Compared with the normal group, the writhing times and writhing score were significantly increased (P<0.05); the endometrial epithelial cells showed vacuolar degeneration, death and hyperemia, the uterine pathological score was increased (P<0.05); the content of serum PGF2α and the ratio of PGF2α/PGE2 were significantly increased (P<0.01), while the content of serum PGE2 was significantly decreased (P<0.01); the expression levels of NMDAR, ERK1/2, p38MAPK and JNK in spinal cord were significantly increased (P<0.05, P<0.01) in the model group. Compared with the model group, the writhing times and writhing score were significantly decreased (P<0.05), the writhing latency was prolonged (P<0.05); the endometrial epithelial cells still showed vacuolar degeneration, death and hyperemia, and the uterine pathological score was decreased (P<0.01); the content of serum PGF2α and the ratio of PGF2α/PGE2 were significantly decreased (P<0.01), while the content of serum PGE2 was significantly increased (P<0.01); the protein expression levels of ERK1/2 and JNK in spinal cord were significantly decreased (P<0.01) in the EA group. EA intervention at SP36 and GV4 has obvious analgesic effect on PDM rats, and its mechanisms may be related to reducing serum prostaglandin, alleviating uterine inflammation, and inhibiting the protein expressions of NMDAR, ERK1/2, p38 MAPK and JNK in spinal cord.

Attempts for increasing Astyanax altiparanae spawning rates and percentage of responsive oocytes

In this study, we aimed to propose changes in the protocol of cultured Astyanax altiparanae hypophysation to increase the maximum ovulation rate of 60% registered previously. To that two consecutive experiments were conducted. In the first experiment, three carp pituitary homogenate (CPH) doses (3, 6, and 9 mg/kg) were administered in a single injection, while in the second experiment, the 6 mg/kg CPH dose was tested either in single or double injections. In the first experiment, a single injection of 3 mg/kg CPH did not induce final oocyte maturation or spawning, while a dose of 6 mg/kg CPH resulted in an increase in the plasma level of prostaglandin (PGF2α) at ovulation. The single higher dose of 9 mg/kg CPH did not improve reproductive performance and even though anticipated the resumption of meiosis it was detrimental to the spawning rate. In the second experiment, the dose of 6 mg/kg CPH fractionated into two injections led to a higher spawning rate, spawning volume per female body mass, frequency of post-ovulatory complexes, and PGF2α concentration at ovulation compared to the single injection. The most effective treatment remained the 6 mg/kg of CPH fractionated into two injections, but still providing very low proportion of ovulated females (∼40 %). Overall, this study indicates that the spawning protocols for this species need to be improved to induce ovulation in a larger number of females and be more potent in those females that respond positively.

Conjugated linoleic acid supplementation changes prostaglandin concentration ratio and alters the expression of genes involved in maternal-fetal recognition from bovine trophoblast cells in vitro

Early embryonic mortality caused by maternal-fetal recognition failure in the three weeks after fertilization represents a major cause of reproductive inefficiency in the cattle industry. Modifying the amounts and ratios of prostaglandin (PG) F2α and PGE2 can benefit the establishment of pregnancy in cattle. Adding conjugated linoleic acid (CLA) to endometrial and fetal cells culture affects PG synthesis, but its effect on bovine trophoblast cells (CT-1) is unknown. The aim of this study was to determine the effects of CLA (a mixture of cis- and trans-9, 11- and −10,12-octadecadienoic acids) on PGE2 and PGF2α synthesis and the expression of transcripts involved with maternal-fetal recognition of bovine trophectoderm. Cultures of CT-1 were exposed to CLA for 24, 48 and 72 h. Transcript abundance was determined by qRT-PCR and hormone profiles were quantified by ELISA. The PGE2 and PGF2α concentrations were reduced in the culture medium of CLA-exposed CT-1 compared to that of unexposed cells. Furthermore, CLA supplementation increased the PGE2:PGF2α ratio in CT-1 and had a quadratic effect (P < 0.05) on the relative expression of MMP9, PTGES2, and PTGER4. The relative expression levels of PTGER4 were reduced (P < 0.05) in CT-1 cultured with 100 μM CLA than in the unsupplemented and 10 μM-CLA groups. Treatment of CT-1 with CLA decreased PGE2 and PGF2α synthesis but a biphasic effect of CLA was observed on the PGE2:PGF2α ratio and relative abundance of transcripts with 10 μM CLA providing maximal improvements in each endpoint. Our data suggest that CLA may influence eicosanoid metabolic process and extracellular matrix remodeling.

Prostaglandin F2α Regulates Adipogenesis by Modulating Extracellular Signal-Regulated Kinase Signaling in Graves' Ophthalmopathy.

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.

Protective role of CoQ10 in reducing the side effects resulting from the use of Tramadol on some immunological variables in the endemic female rabbits

The aim of study to determine out the role of CoQ10 in reducing the side effects from the use of Tramadol on the level of Interlukin IL-6, IL-10 and PGF2α the study included 30 endemic female rabbits, where each group included 5 animals. The results showed increase with a highly significant with (P≤0.01) in the concentration of IL-10 in sera of treated group with tramadol (initial dose) and group treated tramadol (double dose) group treated tramadol (initial dose + CoQ10) and group treated with tramadol (double dose + CoQ10) compare with control.&#x0D; The results showed no significant differences in the concentration of IL-10 in sera of treated group with Co Q10 compare with control. The results revealed high significant increase (P≤0.01) in the concentration of IL-6 in the sera of the treated group with tramadol (double dose) group treated with tramadol (initial dose + COQ10) as compared with the control and the results showed the presence of high significant decrease (P≤0.01) in the concentration of IL-6 in the sera of the group treated with tramadol (initial dose) and treated with group tramadol (double dose + COQ10) compare with control. the results showed there were no significant differences in the concentration of IL-6 in serum of group treated with CoQ10 as compare with control. Results indicated occurrence of high significant increase (P≤0.01) in a concentration of PGF 2α in serum of the group treated with tramadol (initial dose) and group treated with tramadol (double dose)and group treated with tramadol (initial dose + CoQ10) and group treated with tramadol (double dose +CoQ10) compare with control. The results showed presence of a highly significant decrease (P≤0.01) in the concentration of P G F 2α in sera of group treated with CoQ10 as compare with control.

Possible roles of bone morphogenetic protein 4 in regulating endometrial function in cows.

This study investigated the expression dynamics of bone morphogenetic protein 4 (BMP4) and its receptors (BMPR1A, BMPR1B, and BMPR2) in bovine endometrium and examined the physiological function and regulatory mechanism of BMP4 expression. The messenger RNA (mRNA) expression of BMP4 and its receptors was detected in bovine endometrium of both ipsilateral (corpus luteum [CL]-side) and contralateral (non-CL-side) uterine horns during the estrous cycle and early pregnancy. BMP4 protein levels were higher in the endometrial tissues obtained from those cows in early pregnancy than in the estrous cycle. Immunohistochemical analysis showed that BMP4 and its receptors were localized in endometrial epithelial cells. The addition of BMP4 to cultured endometrial epithelial cells did not affect caspase-3/-8 mRNA expression, whereas it significantly inhibited cell proliferation. Both prostaglandin (PG) E2 and PGF2α concentrations in the culture supernatant were decreased when stimulated by BMP4. Furthermore, BMP4 mRNA expression was increased by stimulation with tumor necrosis factor-α (TNF) and interferon-γ (IFNG). In conclusion, BMP4 is produced in bovine endometrial epithelial cells and may contribute to the regulation of cell proliferation and suppression of PG secretion through autocrine or paracrine mechanisms. BMP4 expression in the bovine endometrium may be regulated by TNF and IFNG.

DYNAMICS OF PROAND ANTI-INFLAMMATORY PROSTAGLANDINS IN CASES OF GENERALIZED PERIODONTITIS ACCOMPANIED BY DIFFERENT TYPES OF REACTIVITY OF THE BODY

In terms of socio-economic significance, among the most burning problems of modern dentistry are periodontal diseases. According to modern ideas, in generalized periodontitis, one of the main mechanisms of destruction of the alveolar bone is considered to be an increase in prostaglandin levels. Data on the detection of receptors for PG E2 on the membranes of preosteoblasts and osteoclasts are described. Taking into consideration the effect of prostaglandins F2α and E2 on microvascular and cellular reactions in tissues, we can predict their important role in the development of healing and stabilization of the pathological process in periodontal tissues.&#x0D; The aim of this research was to study the dynamics of proand anti-inflammatory prostaglandins (F2α and E2) in the blood of patients with generalized periodontitis accompanied by normo-, hyperand hyporeactivity of the body after patch surgery.&#x0D; Materials and methods of research. 216 people aged 45 between 55 years old with the diagnosis of generalized periodontitis were examined. Depending on the condition of reactivity of the body, the patients were divided into three groups: 11 normoreaction; 2hyperreaction; 3 hyporeaction. After initial therapy, patch surgery was performed according to the indications. Blood sampling was performed after surgery on the 1st, 2nd, 4th, 6th and 9th day. The content of prostaglandins F2α and E2 was determined by radioimmunoassay.&#x0D; Statistical processing of the obtained digital data was performed using the computer program Statistica 8.0 (STA862D175437Q).&#x0D; Results of the research. The results of this study showed that for patients with generalized periodontitis accompanied by normoreactivity of the body after surgery by an imbalance between the proand antiinflammatory fractions of eicosanoids is typical. On the 1st day, the value of the PG correlation increased, reaching its maximum level on the 2nd day, exceeding the initial value by 1.8 times (p &lt;0.05). This is due to a sharp increase in the content of PG F2α in the blood of patients with generalized periodontitis accompanied by falling concentrations of PG E2. Subsequently, the alignment of the primary balance of prostaglandins was observed on the 9th day, the correlation of PG F2α / PG E2 reached normal values. The change in the correlation of PG F2α / PG E2 in patients with generalized periodontitis accompanied by hyperreactivity of the body was monophasic in nature with its maximum value on the 1st day after surgery. The value of the correlation increased 1.4 times compared to the original (p &lt;0,05) one. On the 2nd day, there was a significant decrease in the correlation of PG F2α / PG E2 to the value below the initial (0.18 ± 0.04). Subsequently, beginning with the 6th day, in the blood of patients with GP with hyperreactivity of the body, the correlation of eicosanoids was close to the initial one. The change in the correlation of PG F2α / PG E2 in patients with generalized periodontitis accompanied by hyporeactivity of the body was monophasic in nature with its maximum values on the 2-4th day after surgery. The value of the correlation became 1.6 times higher compared to the original (p &lt;0,05) one. Subsequently, beginning with the 6th day, in the blood of patients with GP with hyporeactivity of the body the correlation of eicosanoids close to the original was revealed.&#x0D; Conclusion. Correction of altered parameters in patients with generalized periodontitis with impaired (hyperand hyporeactivity) of the body with bringing them to values, typical for normoreactivity is considered to be a condition for optimizing the healing of mucosal wounds after surgery and further stabilization of the process in periodontal tissues.

Macronutrient intake modulates impact of EcoRI polymorphism of ApoB gene on lipid profile and inflammatory markers in patients with type 2 diabetes

We sought to examine whether dietary intakes may affect the relationship between ApoB EcoRI and lipid profile, as well as serum inflammatory markers, in patients with type 2 diabetes (T2DM). This current study consisted of 648 diabetic patients. Dietary intake was calculated by a food frequency questionnaire. Biochemical markers (high-density lipoprotein (HDL), total cholesterol (TC), LDL, TG, CRP, IL-18, PGF2α) were measured based on standard protocols. Genotyping of the Apo-B polymorphisms (rs1042031) was conducted by the PCR–RFLP method. The gene-diet interactions were evaluated using GLMs. In comparison to GG homozygotes, A-allele carriers with above the median -CHO intake (≥ 54 percent of total energy) had considerably greater TC and PGF2a concentrations. Furthermore, as compared to GG homozygotes, A-allele carriers with above the median protein intake (≥ 14 percent of total energy) had higher serum levels of TG (P = 0.001), CRP (P = 0.02), TG/HDL (P = 0.005), and LDL/HDL (P = 0.04) ratios. Moreover, A-allele carriers with above the median total fat intake (≥ 35 percent of total calories) had significantly higher TC level (P = 0.04) and LDL/HDL (P = 0.04) ratios compared to GG homozygotes. Furthermore, when compared to GG homozygotes, A-allele carriers who consumed above the median cholesterol (> 196 mg) had greater TG (P = 0.04), TG/HDL (P = 0.01) ratio, and IL-18 (P = 0.02). Furthermore, diabetic patients with the GA, AA genotype who consume above the median cholesterol had lower ghrelin levels (P = 0.01). In terms of LDL/HDL ratio, ApoB EcoRI and dietary intakes of specific fatty acids (≥ 9 percent for SFA and ≥ 12 percent for MUFA) had significant interaction. LDL/HDL ratio is greater in A-allele carriers with above the median SFA intake (P = 0.04), also when they consumed above the median MUFA this association was inverse (P = 0.04). Our study showed that plasma lipid levels in participants carrying the (AA or AG) genotype were found to be more responsive to increasing the percentage of energy derived from dietary fat, CHO, protein, SFA, and cholesterol consumption. Therefore, patients with a higher genetic susceptibility (AA or AG) seemed to have greater metabolic markers with a higher percentage of macronutrient consumption. Also, ApoB EcoRI correlations with metabolic markers might be attenuated with above the median MUFA consumption.

Prostaglandin 2α Promotes Autophagy and Mitochondrial Energy Production in Fish Hepatocytes.

Fatty liver, characterized by excessive lipid droplet (LD) accumulation in hepatocytes, is a common physiological condition in humans and aquaculture species. Lipid mobilization is an important strategy for modulating the number and size of cellular LDs. Cyclooxygenase (COX)-mediated arachidonic acid derivatives are known to improve lipid catabolism in fish; however, the specific derivatives remain unknown. In the present study, we showed that serum starvation induced LD degradation via autophagy, lipolysis, and mitochondrial energy production in zebrafish hepatocytes, accompanied by activation of the COX pathway. The cellular concentration of PGF2α, but not other prostaglandins, was significantly increased. Administration of a COX inhibitor or interference with PGF2α synthase abolished serum deprivation-induced LD suppression, LD–lysosome colocalization, and expression of autophagic genes. Additionally, exogenous PGF2α suppressed the accumulation of LDs, promoted the accumulation of lysosomes with LD and the autophagy marker protein LC3A/B, and augmented the expression of autophagic genes. Moreover, PGF2α enhanced mitochondrial accumulation and ATP production, and increased the transcript levels of β-oxidation- and mitochondrial respiratory chain-related genes. Collectively, these findings demonstrate that the COX pathway is implicated in lipid degradation induced by energy deprivation, and that PGF2α is a key molecule triggering autophagy, lipolysis, and mitochondrial development in zebrafish hepatocytes.

Effect of metritis on in-vitro uterine contractility in cows during the puerperium

Aim of this study was to determine the effect of metritis on in-vitro uterine contractility. Uteri obtained from 16 euthanized Holstein-Friesian cows were divided into two groups depending on whether metritis was absent (M-, n = 6) or present (M+, n = 10). Four longitudinal and four circular myometrial strips of all uteri were incubated in an organ bath. Spontaneous contractility was recorded in five consecutive 30-minute periods (T1-T5). This was followed by stimulation of one longitudinal and one circular strip with increasing concentrations of oxytocin, prostaglandinF2α (PGF2α), and calcium chloride (each during four 30-minute periods [T6-T9]). Strips in group M+ had higher minimum amplitude (minA) values at T1 and higher minA, mean amplitude (meanA), and area under the curve (AUC) values at T2 than strips in group M- (P ≤ 0.05). In the M+ group, the maximum amplitude (maxA), meanA, and AUC values of circular strips were higher than those of longitudinal strips during spontaneous contractility (T1, T4, and T5; P ≤ 0.05). The minA, meanA, and AUC values for strips in group M+ were higher than those in group M- when exposed to the highest concentration of PGF2α (P ≤ 0.05). During stimulation with PGF2α (T9), longitudinal strips had higher maxA values than the circular strips in group M+ (P ≤ 0.05). Spontaneous and stimulated contractility were temporarily increased in uteri with metritis compared to healthy uteri. Both myometrial layers, especially in uteri with metritis, reacted differently during spontaneous contractility and to stimulation with PGF2α.

Pregnancy maintenance following sequential induced prostaglandin pulses in beef cows

The relationship between the maternal endocrine environment and late embryonic mortality (> 28 d of gestation) in cattle is poorly defined. A definitive rise and alterations in secretion patterns of prostaglandin F2α (PGF2α) concentration without luteal regression is a trademark of this period. The objective was to evaluate whether consecutively induced PGF2α pulses would alter steroid hormone production and luteal blood perfusion potentially influencing pregnancy success. Pregnant beef cows (n = 12) were selected to receive either an oxytocin injection (OT, n = 8) or saline injection (CON, n = 4) on d 30 and 31 of gestation to stimulate sequential prostaglandin releases 24 h apart. Blood samples were collected every 30 min for 1 h before and continuing for 4 h post oxytocin administration. Luteal blood perfusion was measured via Doppler ultrasound at the beginning and end of the OT challenge. Concentrations of prostaglandin F2α metabolite (PGFM) were quantified to show effectiveness of the treatment while concentrations of progesterone, estradiol and pregnancy-associated glycoproteins (PAG) were measured to examine the effect of PGF2α release. Control animals exhibited no changes in any quantified hormone and an expected numerical increase in circulating PAG concentrations. Peak concentrations of PGFM in OT cows were observed 2 h post OT administration and concentrations returned to basal levels by the end of the sampling period. Peak concentrations of PGFM were decreased on d 31 compared to d 30. Following OT administration, progesterone and estradiol concentrations did not change in response to PGF2α release but were decreased on d 31 compared to d 30. There were no changes in luteal blood perfusion in response to PGF release on d 30 or d 31. Repeated PGF2α release may alter steroid hormone production; however, it does not negatively affect pregnancy status during the transition between early and late embryonic development.

The Effects of Prostaglandin E2 Treatment on the Secretory Function of Mare Corpus Luteum Depends on the Site of Application: An in vivo Study.

We examined the effect of prostaglandin (PG) E2 on the secretory function of equine corpus luteum (CL), according to the application site: intra-CL injection vs. an intrauterine (intra-U) administration. Moreover, the effect of intra-CL injection vs. intra-U administration of both luteotropic factors: PGE2 and human chorionic gonadotropin (hCG) as a positive control, on CL function was additionally compared. Mares were assigned to the groups (n = 6 per group): (1) an intra-CL saline injection (control); (2) an intra-CL injection of PGE2 (5 mg/ml); (3) an intra-CL injection of hCG (1,500 IU/ml); (4) an intra-U saline administration (control); (5) an intra-U administration of PGE2 (5 mg/5 ml); (6) an intra-U administration of hCG (1,500 IU/5 ml). Progesterone (P4) and PGE2 concentrations were measured in blood plasma samples collected at −2, −1, and 0 (pre-treatment), and at 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after treatments. Moreover, effects of different doses of PGE2 application on the concentration of total PGF2α (PGF2α and its main metabolite 13,14-dihydro-15-keto-prostaglandin F2α– PGFM) was determined. The time point of PGE2, hCG, or saline administration was defined as hour “0” of the experiment. An intra-CL injection of PGE2 increased P4 and PGE2 concentrations between 3 and 4 h or at 3 and 12 h, respectively (p < 0.05). While intra-U administration of PGE2 elevated P4 concentrations between 8 and 24 h, PGE2 was upregulated at 1 h and between 3 and 4 h (p < 0.05). An intra-CL injection of hCG increased P4 concentrations at 1, 6, and 12 h (p < 0.05), while its intra-U administration enhanced P4 and PGE2 concentrations between 1 and 12 h or at 3 h and between 6 and 10 h, respectively (p < 0.05). An application of PGE2, dependently on the dose, supports equine CL function, regardless of the application site, consequently leading to differences in both P4 and PGE2 concentrations in blood plasma.

Docosahexaenoic Acid Selectively Suppresses U46619- and PGF2α-Induced Contractions in Guinea Pig Tracheal Smooth Muscles.

We investigated the potential inhibitory effects of docosahexaenoic acid (DHA) on the contractions of guinea pig tracheal smooth muscles in response to U46619 (a thromboxane A2 (TXA2) mimetic) and prostaglandin F2α (PGF2α) to examine whether this n-3 polyunsaturated fatty acid suppresses prostanoid-induced tracheal contractions. DHA (3 × 10-5 M) significantly suppressed tracheal contractions elicited by lower concentrations of U46619 (10-8 M) and PGF2α (5 × 10-7 M) (vs. control), although it did not suppress the contractions induced by higher concentrations (U46619: 10-7 M; PGF2α: 10-5 M). Supporting these findings, DHA (4 × 10-5 M/6 × 10-5 M) shifted the concentration-response curves for U46619 (10-9-10-6 M) and PGF2α (10-8-10-5 M) to the right. However, the slope of the regression line in the Schild plot of DHA vs. U46619/PGF2α was larger than unity. The tracheal contractions induced by U46619 (10-8 M) and PGF2α (5 × 10-7 M) were significantly suppressed by the prostanoid TP receptor antagonist SQ 29,548 (10-6 M) (vs. ethanol-treated). In contrast, DHA (4 × 10-5 M) did not show significant inhibitory effects on the contractions induced by acetylcholine (10-8-10-4 M), histamine (10-8-10-4 M), and leukotriene D4 (10-11-10-7 M) (vs. ethanol-treated). These findings indicate that DHA selectively suppresses tracheal contractions induced by U46619 and PGF2α. Therefore, DHA may be a useful therapeutic agent against asthma associated with tracheal/bronchial hyper-constriction caused by prostanoids including TXA2 and PGF2α.

MODERN DIAGNOSTIC CRITERION FOR ESTABLISHING THE REGIONAL ORIGIN OF BLOOD IN SEXUAL CRIMES

The aim: Determination of regional blood origin in cases of sexual violence, establishing the possibility of using prostaglandin F2alpha as a marker of blood of menstrual origin. Materials and methods: The material for the study were samples of vaginal fluid, menstrual blood and capillary blood from females, the age distribution of women was carried out according to the gynecological classification according to the age periods of women’s lives depending on the functional state of their reproductive system: the first group – women at the age of 18-29, the second group – women at the age of 30-45. Results: Among objects of biological origin, fluids, especially blood, occupy an important place. The content of PGF2α has age fluctuations: its content is higher by 6-12% in women aged 30-45 than in women 18-29 years old. PGF2α levels above 13.1 ng / mg of dry tissue are a reliable sign of blood of menstrual origin, which is very important in determining the regional origin of blood in forensic examinations for sexual violence / sexual crimes. Conclusions: In cases of sexual violence against women, in addition to recording external harm, attention should also be paid to the examination of objects of biological origin, identification by species, sex, regional, organ or cell.