Effect of exogenous oestrogen treatment frequency on induction of artificial lactation in pseudopregnant sows.

In this study, we examined whether the frequency of exogenous oestrogen treatment affects the induction of artificial lactation and milk production. Furthermore, we analysed changes in milk components obtained from artificially lactating sows. Pseudopregnant induced by treatment with 30 mg of estradiol dipropionate (EDP) on Day 10 (Day 0 = the last day of estrus) were divided into three groups: those administered 5 mg of EDP once on Day 39 (n = 5), twice on Days 32 and 39 (n = 5) and three times on Days 25, 32 and 39 (n = 6). All animals were treated with prostaglandin F2α (PGF2α) on Day 46 for induced lactation. Artificial lactation was induced in 66.7%-80.0% of sows, and the EDP treatment frequency before PGF2α administration had no significant effect on either the induction rate of artificial lactation or the milk yield during the experimental period. The milk composition (levels of crude protein, crude fat, crude ash, lactose and immunoglobulin) did not differ among the groups. In conclusion, the number of EDP treatments prior to PGF2α administration had no effect on either the efficiency of artificial lactation induction or milk production.

Cellular senescence mediates hexavalent chromium-associated lung function decline: Insights from a structural equation Model.

There is sufficient evidence suggesting that exposure to hexavalent chromium [Cr(VI)] can cause a decline in lung function and the onset of lung diseases. However, no studies have yet explored the underlying mechanisms of these effects from various perspectives such as systemic inflammation, oxidative stress, and cellular senescence, simultaneously. This cross-sectional study was conducted among 304 workers engaged in chromate production and processing in China. Urine was used for detection of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α), while RNA and DNA extraction from peripheral blood cells was used for detection of mRNA, telomere length, and ribosomal DNA copy numbers (rDNA CNs). A 2.7-fold elevation in blood chromate (Cr) corresponded to a 7.86% (95% CI: 2.57%, 13.42%) rise in urinary 8-OHdG and a 4.14% (0.02%, 8.42%) increase in urinary 8-iso-PGF2α, indicating that exposure to chromates can cause oxidative stress. Furthermore, strong correlations emerged between blood Cr concentration and mRNA levels of P16, P21, TP53, and P15 in the cellular senescence pathway. Simultaneously, a 2.7-fold elevation in blood Cr associated with a -5.47% (-8.72%, -2.1%) change in telomere length, while rDNA CNs (5S, 5.8S, 18S, and 28S) changed by -3.91% (-7.99%, 0.34%), -9.4% (-15.73%, -2.6%), -8.06% (-14.01%, -1.69%), and -5.86% (-10.67%, -0.78%), respectively. Structural equation model highlighted that cellular senescence exerted significant indirect effects on Cr(VI)-associated lung function decline, with a mediation proportion of 23.3%. This study provided data supporting for 8-iso-PGF2α, telomere length, and rDNA CNs as novel biomarkers of chromate exposure, emphasizing the significant role of cellular senescence in the mechanism underlying chromate-induced lung function decline.

The influence of physical activity, body mass index and urinary levels of prostaglandin (PGF2α) with the incidence of primary dysmenorrhea in adolescents.

OBJECTIVE: This study aims to investigate the effect of physical activity, body mass index (BMI), and levels of prostaglandins (PGF2α) urine on the occurrence of dysmenorrhea in adolescents. METHODS: A total of 128 female students included in the study. The study was conducted from January to March 2023 using a cross-sectional design. This study utilized the Menstrual Symptom Questionnaire (MSQ) and gynecological examination with ultrasonography. The urinary prostaglandin (PGF2α) was measured using the enzyme linked immuno sorbent assay (ELISA). Data were analyzed using the chi-square test and logistic regression test. RESULTS: The age range of the participants included in the study was 14-17, with a mean age of 15.85 ± 0.65. There was an correlation between physical activity, BMI, and urinary prostaglandin (PGF2α) levels with the incidence of dysmenorrhea in adolescents (p < 0.001). In multivariate analysis, it revealed that underweight, and had a high urinary prostaglandin significant correlated to primary dysmenorrhea with odds ratio 4.78 (95% confidence interval [CI] 1.98-11.54) and 4.88 (95% CI 1.98-12.08), respectively. High physical activity and overweight was not associated with incidence of dysmenorrhea in adolescents. CONCLUSION: This study provides valuable insights into the correlation between physical activity, BMI, and levels of prostaglandins (PGF2α) in urine. A high level of urinary prostaglandin was found to be the most influential factor in the incidence of primary dysmenorrhea in adolescents. By addressing factors associated with dysmenorrhea in adolescents, healthcare professionals can potentially enhance well-being by reducing menstrual pain and encouraging a healthy lifestyle to prevent dysmenorrhea.

Effect of photobiomodulation on alleviating primary dysmenorrhea caused by PGF2α.

Photobiomodulation (PBM) has attracted widespread attention in suppressing various pain and inflammation. Primary dysmenorrhea (PD) primarily occurs in adolescents and adult females, and the limited effectiveness and side effects of conventional treatments have highlighted the urgent need to develop and identify new adjunct therapeutic strategies. In this work, the results of pain and PGs demonstrated that 850 nm, 630 nm, and 460 nm all exhibited pain inhibition, decreased PGF2α and upregulated PGE2, while 630 nm PBM has better effectiveness. Then to explore the underlying biological mechanisms of red light PBM on PD, we irradiated prostaglandin-F2α induced HUSM cells and found that low-level irradiance can restore intracellular calcium ion, ROS, ATP, and MMP levels to normal levels. And, red light enhanced cell viability and promoted cell proliferation for normal HUSM cells. Therefore, this study proposes that red light PBM may be a promising approach for the future clinical treatment of PD.

A General Catalyst Controlled Route to Prostaglandin F2α.

We report a general, catalyst-controlled route to prostaglandin F2α and its analogues. The approach uses a Rh-catalyzed dynamic kinetic asymmetric Suzuki-Miyaura coupling reaction between a racemic bicyclic allyl chloride and alkenyl boronic esters bearing chiral alcohols to give cyclopentyl intermediates bearing 3 contiguous stereocenters. The route provides advanced intermediates in 99% ee as a single diastereoisomer in all cases examined, with the absolute stereochemistry of the cyclopentane core controlled by the ligand. Intermediates that could be used to produce prostaglandin analogues such as bimatoprost, latanoprost, fluprostenol, and cloprostenol were synthesized. The final two stereocenters were installed via Pd-catalyzed Tsuji-Trost alkylation and iodolactonization. The synthesis of PG F2α was achieved in 19% yield in 16 longest linear steps.

Quantification of Plasma 8-Isoprostane by High-Performance Liquid Chromatography with Tandem Mass Spectrometry in a Case-Control Study of Lung Cancer.

AIM: 8-iso-prostaglandin F2α is a biomarker of lipid peroxidation, and one of the most commonly used measures of oxidative stress. It is an established biomarker of lung cancer risk. It is commonly measured by enzyme-linked immunosorbent assay. Given its importance, we developed a stable isotope dilution UPLC-tandem mass spectrometric method for the rapid determination of 8-isoprostane in blood. METHODS: We tested the discriminatory capability of the method in 49 lung cancer patients, 55 benign lung nodule patients detected by chest X-ray, and 41 patients with chronic obstructive pulmonary disease (COPD) or asthma. RESULTS: Significant differences were found in mean 8-isoprostane levels between the three groups (p = 0.027), and post-hoc tests found higher levels in the lung cancer patients than in patients with benign nodules (p = 0.032) and COPD/asthma (p = 0.014). The receiving operating characteristic area under the curve (AUC) was 0.69 for differentiating the lung cancer group from the benign nodule group, and 0.7 for differentiating from the COPD/asthma group. CONCLUSIONS: The UPLC-MS/MS-based method is an efficient analytical tool for measuring 8-isoprostane plasma concentrations. The results suggest exploring its utility as a marker for early lung cancer screening.

Elevated 8-isoprostane concentration is associated with thromboembolic events in patients with atrial fibrillation.

BACKGROUND: Enhanced oxidative stress occurs in atrial fibrillation (AF), however its impact on the efficacy and safety of anticoagulation is unknown. We sought to evaluate whether 8-isoprostaglandin F2 (8-isoprostane) levels are associated with clinical outcomes in anticoagulated AF patients. METHODS: In a study involving 243 AF patients (median age 69 years), we measured serum 8-isoprostane, along with prothrombotic markers, including plasma fibrin clot permeability, clot lysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor (VWF), and fibrinolytic proteins. Ischemic cerebrovascular events, major bleeding, and death were recorded during a median follow-up of 53 months while on anticoagulation, largely on non-vitamin K antagonist oral anticoagulants (NOACs). RESULTS: Increased 8-isoprostane levels were observed in women, in patients with arterial hypertension, and those with paroxysmal or persistent AF. Patients with 8-isoprostane levels ≥559 pg/mL (the top quartile) compared with those with 8-isoprostane <250 pg/mL (the bottom quartile) had higher fibrinogen, lower VWF, higher plasminogen activator inhibitor 1, along with lower fibrin clot permeability with no difference in CHA2DS2-VASc score, CLT or ETP. Patients who experienced thromboembolic events (n = 20, 1.9%/year) had 48.6% higher 8-isoprostane concentrations compared to the remainder (P <0.01). Levels of 8-isoprostane >459 pg/mL based on the optimal cut-off value were associated with thromboembolic events during follow-up (hazard ratio 2.87, 95% confidence interval 1.17-7.03, P = 0.02). There were no associations between 8-isoprostane and major bleeding (2.0%/year) or all-cause mortality (1.9%/year). CONCLUSIONS: Increased 8-isoprostane levels partly through altered fibrin clot structure are associated with thromboembolic events despite anticoagulant therapy in AF patients.

The F2-isoprostane 8-iso-PGF2α attenuates atherosclerotic lesion formation in Ldlr-deficient mice - Potential role of vascular thromboxane A2 receptors.

The F2-isoprostane 8-iso-PGF2α (also known as 15-F2t-isoprostane, iPF2α-III, 8-epi PGF2α, 15(S)-8-iso-PGF2α, or 8-Isoprostane), a thromboxane A2 receptor (TP) agonist, stable biomarker of oxidative stress, and risk marker of cardiovascular disease, has been proposed to aggravate atherogenesis in genetic mouse models of atherosclerotic vascular disease. Moreover, the TP plays an eminent role in the pathophysiology of endothelial dysfunction, atherogenesis, and cardiovascular disease. Yet it is unknown, how the TP expressed by vascular cells affects atherogenesis or 8-iso-PGF2α-related effects in mouse models of atherosclerosis. We studied Ldlr-deficient vascular endothelial-specific (EC) and vascular smooth muscle cell (VSMC)-specific TP knockout mice (TPECKO/Ldlr KO; TPVSMCKO/Ldlr KO) and corresponding wild-type littermates (TPWT/Ldlr KO). The mice were fed a Western-type diet for eight weeks and received either 8-iso-PGF2α or vehicle infusions via osmotic pumps. Subsequently, arterial blood pressure, atherosclerotic lesion formation, and lipid profiles were analyzed. We found that VSMC-, but not EC-specific TP deletion, attenuated atherogenesis without affecting blood pressure or plasma lipid profiles of the mice. In contrast to a previous report, 8-iso-PGF2α tended to reduce atherogenesis in TPWT/Ldlr KO and TPEC KO/Ldlr KO mice, again without significantly affecting blood pressure or lipid profiles of these mice. However, no further reduction in atherogenesis was observed in 8-iso-PGF2α-treated TPVSMC KO/Ldlr KO mice. Our work suggests that the TP expressed in VSMC but not the TP expressed in EC is involved in atherosclerotic lesion formation in Ldlr-deficient mice. Furthermore, we report an inhibitory effect of 8-iso-PGF2α on atherogenesis in this experimental atherosclerosis model, which paradoxically appears to be related to the presence of the TP in VSMC.

Role of urinary H2O2, 8-iso-PGF2α, and serum oxLDL/ß2GP1 complex in the diabetic kidney disease.

Oxidant species is reported as a major determinant in the pathophysiology of diabetic kidney disease. However, reactive oxygen species (ROS) formation in the initial phase and progressing phase of diabetic kidney disease remains unclear. Therefore, we conducted this study to find out what ROS and their modified product are associated with eGFR in type 2 diabetes mellitus (T2DM) patients. A cross-sectional study was performed on 227 T2DM patients. The study subjects were divided into three groups based on their eGFR stage (Group 1, eGFR > 89 ml/min/1.73 m2; Group 2, eGFR = 60-89 ml/min/1.73 m2; and Group 3, eGFR < 60 ml/min/1.73 m2). Enzyme-linked immunosorbent assay (ELISA) was used to measure serum oxLDL/ß2GPI complex and urinary 8-iso-PGF2α, while ferrous ion oxidation xylenol orange method 1 (FOX-1) was used to measure urinary hydrogen peroxide (H2O2). H2O2 significantly decreased across the groups, whereas OxLDL/ß2GPI complex increased, but not significant, and there was no trend for 8-iso-PGF2α. Consistently, in the total study population, only H2O2 showed correlation with eGFR (r = 0.161, p = 0.015). Multiple linear regression analysis showed that significant factors for increased eGFR were H2O2, diastolic blood pressure, and female. Whereas increased systolic blood pressure and age were significant factors affecting the decrease of eGFR. We also found that urinary H2O2 had correlation with serum oxLDL/ß2GPI complex in total population. This finding could lead to further research on urinary H2O2 for early detection and research on novel therapies of diabetic kidney disease.

Isoprostane-8 and GDF-15 as novel markers of post-PE syndrome: Relation with prothrombotic factors.

BACKGROUND: Post-pulmonary embolism (PE) syndrome occurs in up to 50% of PE patients. The pathophysiology of this syndrome is obscure. OBJECTIVE: We investigated whether enhanced oxidative stress and prothrombotic state may be involved in post-PE syndrome. METHODS: We studied 101 normotensive noncancer PE patients (aged 56.5 ± 13.9 years) on admission, after 5-7 days and after a 3-month anticoagulation, mostly with rivaroxaban. A marker of oxidative stress, 8-isoprostane, endogenous thrombin potential, fibrinolysis proteins, clot lysis time (CLT) and fibrin clot permeability (Ks ), along with PE biomarkers, were determined. RESULTS: Patients who developed the post-PE syndrome (n = 31, 30.7%) had at baseline 77.6% higher N-terminal brain natriuretic propeptide and 46.8% higher growth differentiation factor 15, along with 14.1% longer CLT associated with 34.4% higher plasminogen activator inhibitor-1 as compared to subjects without post-PE syndrome (all P < .05). After 5-7 days, only hypofibrinolysis was noted in post-PE syndrome patients. When measured at 3 months, prolonged CLT and reduced Ks were observed in post-PE syndrome patients, accompanied by 23.8% higher growth differentiation factor 15 and 35.8% higher plasminogen activator inhibitor-1 (all P < .05). 8-isoprostane levels ≥108 pg/ml (odds ratio=4.36; 95% confidence interval 1.63-12.27) and growth differentiation factor 15 ≥ 1529 pg/ml (odds ratio=3.89; 95% confidence interval 1.29-12.16) measured at 3 months were associated with higher risk of developing post-PE syndrome. CONCLUSIONS: Enhanced oxidative stress and prothrombotic fibrin clot properties could be involved in the pathogenesis of the post-PE syndrome. Elevated growth differentiation factor 15 assessed at 3 months might be a new biomarker of this syndrome.

Quantile-specific heritability of 8-isoprostane and the modulating effects of smoking, alcohol, cardiovascular disease and diabetes on 8-isoprostane-gene interactions.

BACKGROUND: Urinary 8-isoprostane provides a significantly heritable measure of oxidative stress. Prior reports suggest that genetic variants may modulate oxidative stress due to smoking, other environmental factors, and disease. Alternatively, these apparent modulations may reflect a dependence of genetic effects on 8-isoprostane concentrations. METHOD: To test whether genetic effects on 8-isoprostane concentrations are quantile-dependent, quantile-specific offspring-parent (ßOP) and full-sib regression slopes (ßFS) were estimated by applying quantile regression to the age- and sex-adjusted creatinine-standardized urinary 8-isoprostane concentrations of Framingham Heart Study families. Quantile-specific heritabilities were calculated as h2 = 2ßOP/(1+rspouse) and h2 = {(1+8rspouseßFS)0.5-1}/(2rspouse)). RESULTS: Spouse 8-isoprostane concentrations were weakly concordant (rspouse = 0.06). 8-isoprostane heritability (h2±SE) increased significantly with increasing percentiles of its distribution (Plinear trend = 0.0009, Pquadratic trend = 0.0007, Pcubic trend = 0.003) when estimated from ßOP, and when estimated from ßFS (Plinear trend = 0.005, Pquadratic trend = 0.09, Pcubic trend = 0.06). Compared to the 10th percentile, ßOP-estimated h2 was over 22-fold greater at the 90th percentile (Pdifference = 9.2 × 10-5), and 5.3-fold greater when estimated from ßFS (Pdifference = 0.004). Significantly higher 8-isoprostane heritability in smokers than nonsmokers (0.352 ± 0.147 vs. 0.061 ± 0.036, Pdifference = 0.01), and heavier than lighter drinkers (0.449 ± 0.216 vs. 0.078 ± 0.037, Pdifference = 0.01) were eliminated when corrected for the higher 8-isoprostane concentrations of the smokers and heavier drinkers. CONCLUSION: Heritability of oxidative stress as measured by 8-isoprostane is quantile-dependent, which may contribute to the larger reported effects on oxidative stress by UCP2 -866G > A, IL6 -572C > G and LTA 252A > G polymorphisms in smokers than nonsmokers, by the UCP2 -866G > A polymorphism in coronary heart disease patients, by the ESRRG rs1890552 A > G polymorphism in type 2 diabetics, by the CYBA 242C > T polymorphism after exercise training, by the PLIN 11482G > A/14995A > T haplotype before weight loss, and by the CYBA -930A > G and GSTP1 I105V haplotypes in patients with pulmonary edema.

Prostaglandin analog effects on cerebrospinal fluid reabsorption via nasal mucosa.

INTRODUCTION: Cerebrospinal fluid (CSF) outflow has been demonstrated along nasal lymphatics via olfactory nerve projections; flow may be increased by stimulating lymphatic contractility using agents such as noradrenaline and the thromboxane A2 analog U46619. Lymphatics elsewhere in the body show increased contractility upon exposure to the prostaglandin F2alpha analog isoprostane-8-epi-prostaglandin. We investigated the ability of ophthalmic prostaglandin F2alpha analogs to increase CSF outflow when applied to the nasal mucosa by inhalation. METHODS: Latanoprost (0.1, 0.5, or 1mg/ml), bimatoprost (0.3 or 3mg/ml), travoprost (0.04 or 0.4mg/ml), latanoprostene bunod (0.24 or 2.4mg/ml), tafluprost (0.25 or 2.5mg/ml), or control vehicle (10% DMSO) was administered to awake adult C57B/6 mice by nasal inhalation of 2µl droplets. Multiday dosing (daily for 3 days) of latanoprost also was evaluated. A total of 81 animals were studied including controls. General anesthesia was induced by injection, and fluorescent tracer (AlexaFluor647-labelled ovalbumin) was injected under stereotaxic guidance into the right lateral ventricle. Nasal turbinate tissue was harvested and homogenized after 1 hour for tracer detection by ELISA and fluorometric analysis. RESULTS: Inhalation of latanoprost 0.5mg/ml and 1mg/ml led to a 11.5-fold increase in tracer recovery from nasal turbinate tissues compared to controls (3312 pg/ml vs 288 pg/ml, p<0.001 for 0.5mg/ml; 3355 pg/ml vs 288 pg/ml, p<0.001 for 1mg/ml), while latanoprost 0.1 mg/ml enhanced recovery 6-fold (1713 pg/ml vs 288 pg/ml, p<0.01). Tafluprost 0.25mg/ml and bimatoprost 0.3mg/ml showed a modest (1.4x, p<0.05) effect, and the remaining agents showed no significant effect on tracer recovery. After 3 days of daily latanoprost treatment and several hours after the last dose, a persistently increased recovery of tracer was found. CONCLUSIONS: Prostaglandin F2alpha analogs delivered by nasal inhalation resulted in increased nasal recovery of a CSF fluorescent tracer, implying increased CSF outflow via the nasal lymphatics. The greatest effect, partially dose-dependent, was observed using latanoprost. Further studies are needed to determine the efficacy of these agents in reducing ICP in short and long-term applications.

Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia.

Mild hypoglycemia is common in clinical practice. Severe hypoglycemia results in heat shock protein and associate co-chaperone changes. Whether mild prolonged hypoglycemia elicits a similar response with inflammatory and oxidative-stress responses compared with a severe hypoglycemic event is unclear; therefore, this pilot exploratory study was undertaken. We performed a case-control induced hypoglycemia clamp study, maintaining blood glucose at 2.8 mmol/L (50 mg/dL) for 1 h in 17 subjects (T2D (n = 10); controls (n = 7)). Blood sampling was performed at baseline, hypoglycemia, and 24 h; slow off-rate modified aptamer (SOMA)-scan plasma protein analysis of HSP-related proteins, inflammatory stress markers, and oxidative stress markers was performed. In total, 16 HSPs were analyzed. At baseline, TLR4:MD-2 complex was elevated (p = 0.01), whilst HSPA8 was lower (p < 0.05) in T2D. At hypoglycemia, UBE2N, STIP1, and UBE2L3 increased (all p < 0.05), whilst TLR4:MD-2 and HSPA8 decreased (p < 0.05) in T2D versus baseline. In follow-up after hypoglycemia, HSPs normalized to baseline by 24 h, except UBE2L3 (p < 0.05), which was decreased in controls versus baseline. Correlation of altered inflammatory markers with HSPs revealed the following: at baseline, TLR4:MD-2 correlated with CXCL10 (p < 0.01) and SIGLEC1 (p < 0.05) in controls; HSPA8 negatively correlated with IL5 (p < 0.05) in T2D. A negative correlation between urinary isoprostane 8-iso PGF2α, a marker of oxidative stress, and HSPA1A was seen at 24 h in T2D only (p < 0.05). In conclusion, the HSP changes seen for mild prolonged hypoglycemia were similar to those previously reported for a severe event. However, mild prolonged hypoglycemia appeared to elicit an increased inflammatory response that was associated with heat shock and related proteins.

Efficacy and Side Effects of Low Single Doses of Cloprostenol Sodium or Dinoprost Tromethamine to Induce Luteolysis in Donkeys.

Due to the limited literature available evaluating doses of Prostaglandin F2α in donkeys, doses for horses have been extrapolated and used as guidelines. This study aimed to assess the efficacy and side effects of four different cloprostenol sodium and dinoprost tromethamine doses to induce luteolysis in jennies. Sixty-three cycles of seven Jennies (nine cycles per jenny) were used in this study. Seven days after ovulation, jennies randomly received one of the treatments in a crossover design as follows: Control, no treatment was administered; C1, 250 µg of cloprostenol sodium (CS, Estrumate , Merck Animal Health, USA); C2, 125 µg of CS; C3, 65.5 µg of CS, C4, 37.5 µg of CS; DT1, 5 mg of dinoprost tromethamine (DT, Lutalyse, Zoetis, USA); DT2, 2.5 mg of DT; DT3, 1.25 mg of DT; DT4, 0.625 mg of DT. Jennies were monitored for 30 minutes following treatment, and adverse effects were recorded. The measurement of the corpus luteum (CL) and the length of the estrous cycle were recorded. All DT and CS treatment doses were effective (P < .0001) in reducing the estrous cycle length compared to jenny's Control cycle. The CL volume was decreased in all treated groups one day after treatment (P < .05). The adverse effects were reduced as the dose of both Prostaglandin F2α analogs were reduced. In conclusion, a single low dose of dinoprost tromethamine (0.625 mg) or cloprostenol sodium (37.5 µg) can induce luteolysis and shorten the estrous length in jennies producing fewer adverse effects.

Prostaglandins in biofluids in pregnancy and labour: A systematic review.

Prostaglandins are thought to be important mediators in the initiation of human labour, however the evidence supporting this is not entirely clear. Determining how, and which, prostaglandins change during pregnancy and labour may provide insight into mechanisms governing labour initiation and the potential to predict timing of labour onset. The current study systematically searched the existing scientific literature to determine how biofluid levels of prostaglandins change throughout pregnancy before and during labour, and whether prostaglandins and/or their metabolites may be useful for prediction of labour. The databases EMBASE and MEDLINE were searched for English-language articles on prostaglandins measured in plasma, serum, amniotic fluid, or urine during pregnancy and/or spontaneous labour. Studies were assessed for quality and risk of bias and a qualitative summary of included studies was generated. Our review identified 83 studies published between 1968-2021 that met the inclusion criteria. As measured in amniotic fluid, levels of PGE2, along with PGF2α and its metabolite 13,14-dihydro-15-keto-PGF2α were reported higher in labour compared to non-labour. In blood, only 13,14-dihydro-15-keto-PGF2α was reported higher in labour. Additionally, PGF2α, PGF1α, and PGE2 were reported to increase in amniotic fluid as pregnancy progressed, though this pattern was not consistent in plasma. Overall, the evidence supporting changes in prostaglandin levels in these biofluids remains unclear. An important limitation is the lack of data on the complexity of the prostaglandin pathway outside of the PGE and PGF families. Future studies using new methodologies capable of co-assessing multiple prostaglandins and metabolites, in large, well-defined populations, will help provide more insight as to the identification of exactly which prostaglandins and/or metabolites consistently change with labour. Revisiting and revising our understanding of the prostaglandins may provide better targets for clinical monitoring of pregnancies. This study was supported by the Canadian Institutes of Health Research.

Associations of plasma 8-iso-prostaglandin F2αlevels with fasting blood glucose (FBG) and intra-abdominal fat (IAF) area in various Glycometabolism populations.

BACKGROUND: This study aimed to investigate the differences in oxidative stress (OS) levels represented by 8-iso-prostaglandin F2α (8-iso-PGF2α) and analyze its correlation with the intra-abdominal fat (IAF) area and the glycolipid index. METHODS: We recruited a total of 160 eligible subjects. According to the blood glucose levels and the T2DM duration, subjects were divided into three groups: Type 2 Diabetes (T2DM) group, Prediabetic group, and Normal glucose-tolerance (NC) group, containing 66, 41, 53 patients, respectively. T2DM groups were additionally divided into a new-onset T2DM group including 29 patients and a non-new-onset T2DM group including 37 patients. General clinical data and biochemical indicators were collected. Intra-abdominal fat (IAF) was measured by MRI. 8-iso-PGF2α was measured by ELISA. RESULTS: Compared with the NC group, levels of systolic blood pressure (SBP), waist-to-hip ratio (WHR), FBG, 2 h postprandial glycemia(2hPG), 2 h insulin (2 h INS), IAF area, HOMA-IR, and 8-iso-PGF2α increased, and high-density lipoprotein cholesterol (HDL-C) decreased in T2DM groups and Prediabetic group (P < 0.05). The 2 h INS level was the highest in the Prediabetic group; 2hPG, and IAF area were the highest in the new-onset T2DM group; WHR, FBG, HOMA-IR and 8-iso-PGF2α were the highest in the non-new-onset T2DM group. Multiple stepwise regression analysis identified IAF area and FBG as the strongest and independent determinant of 8-iso-PGF2α (P < 0.01). CONCLUSIONS: In various glycometabolism populations, 8-iso-PGF2α is significantly correlated with FBG and IAF, this suggests that high blood glucose and abdominal obesity can increase the damage related to the OS in vivo.

Oxidative Stress and Its Related Factors in Latent Autoimmune Diabetes in Adults.

AIMS: Few research was reported to explore oxidative stress in individuals with latent autoimmune diabetes in adults (LADA). Therefore, our goal is to study oxidative stress and related factors in LADA patients. METHODS: In this study, 250 Chinese inpatients were diagnosed with LADA (n = 110) and type 2 diabetes mellitus (n = 140) and 140 healthy volunteers were recruited. Moreover, individuals with LADA were followed for 6 months to evaluate whether short-term glycemic control during hospitalization can improve oxidative stress. Clinical and laboratory measurements of height, weight, blood pressure, glycosylated hemoglobin (HbA1c), blood lipids, 8-isoprostaglandin F2α (8-iso-PGF2α), and superoxide dismutase (SOD) were performed. Stepwise multiple regression analyses were used to assess factors that related to oxidative stress in individuals with LADA. RESULTS: Compared with patients with type 2 diabetes, individuals with LADA have better oxidative stress and worse oxidative stress than healthy volunteers. After multiple regression analyses, systolic blood pressure, HbA1c, duration of diabetes, and diabetic retinopathy were associated with 8-iso-PGF2α and HbA1c. Diabetic retinopathy and diabetic ketosis were associated with SOD in individuals with LADA. Our results also revealed that, after 6 months of follow-up, oxidative stress was improved to some extent in persons with LADA. CONCLUSIONS: Our results show that compared with type 2 diabetes, LADA means less oxidative stress, and compared with healthy volunteers, it means more oxidative stress. Systolic blood pressure, HbA1c, duration of diabetes, diabetic retinopathy, and ketosis were associated with oxidative stress in individuals with LADA. Furthermore, short-term glycemic control can improve oxidative stress to some extent in individuals with LADA.

Bradykinin Protects Human Endothelial Progenitor Cells from High-Glucose-Induced Senescence through B2 Receptor-Mediated Activation of the Akt/eNOS Signalling Pathway.

BACKGROUND: Circulating endothelial progenitor cells (EPCs) play important roles in vascular repair. However, the mechanisms of high-glucose- (HG-) induced cord blood EPC senescence and the role of B2 receptor (B2R) remain unknown. METHODS: Cord blood samples from 26 patients with gestational diabetes mellitus (GDM) and samples from 26 healthy controls were collected. B2R expression on circulating CD34+ cells of cord blood mononuclear cells (CBMCs) was detected using flow cytometry. The plasma concentrations of 8-isoprostaglandin F2α (8-iso-PGF2α) and nitric oxide (NO) were measured. EPCs were treated with HG (40 mM) alone or with bradykinin (BK) (1 nM). The B2R and eNOS small interfering RNAs (siRNAs) and the PI3K antagonist LY294002 were added to block B2R, eNOS, and PI3K separately. To determine the number of senescent cells, senescence-associated ß-galactosidase (SA-ß-gal) staining was performed. The level of mitochondrial reactive oxygen species (ROS) in EPCs was assessed by Mito-Sox staining. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assays. Mitochondrial DNA (mtDNA) copy number and the relative length of telomeres were detected by real time-PCR. The distribution of human telomerase reverse transcriptase (hTERT) in the nucleus, cytosol, and mitochondria of EPCs was detected by immunofluorescence. The expression of B2R, p16, p21, p53, P-Ser473AKT, T-AKT, eNOS, and hTERT was demonstrated by Western blot. RESULTS: B2R expression on circulating CD34+ cells of CBMCs was significantly reduced in patients with GDM compared to healthy controls. Furthermore, B2R expression on circulating CD34+ cells of CBMCs was inversely correlated with plasma 8-iso-PGF2α concentrations and positively correlated with plasma NO levels. BK treatment decreased EPC senescence and ROS generation. Furthermore, BK treatment of HG-exposed cells led to elevated P-Ser473AKT and eNOS protein expression compared with HG treatment alone. BK reduced hTERT translocation in HG-induced senescent EPCs. B2R siRNA, eNOS siRNA, and antagonist of the PI3K signalling pathway blocked the protective effects of BK. CONCLUSION: BK, acting through PI3K-AKT-eNOS signalling pathways, reduced hTERT translocation, increased the relative length of telomeres while reducing mtDNA copy number, and finally protected against EPC senescence induced by HG.

Serum 8-isoprostane levels in patients with resistant oral lichen planus before and after treatment with lycopene: a randomized clinical trial.

BACKGROUND: Oral lichen planus is an autoimmune disease in which topical steroids are the first line of treatment. The adverse effects of systemic corticosteroids prescribed for resistant oral lichen planus cases advocate alternative modalities. Lycopene is an antioxidant with a wide range of beneficial properties. This trial aimed to evaluate the effect of pure lycopene as compared to systemic corticosteroids (Prednisolone) on the symptoms, signs and oxidative stress in patients with erosive oral lichen planus recalcitrant to topical steroids. METHODS: Twenty patients were randomly divided into the test (lycopene) and control (corticosteroids) groups. Numeric rating scale and Escudier et al. (Br J Dermatol 4:765-770, 2007. https://doi.org/10.1111/j.1365-2133.2007.08106.x ) lesion scores were assessed at baseline and weeks 4 and 8 from baseline. Serum levels of 8-isoprostane were measured in all patients at baseline and at the end of treatment (week 8). RESULTS: There was a significant reduction in signs and symptoms after the end of treatment in each group. However, no significant difference was found between the lycopene and the corticosteroids group. Moreover, a significant reduction in 8-isoprostane levels was observed in the lycopene group from baseline and as compared to the control group. CONCLUSIONS: Based on the study results, lycopene is a safe and effective therapeutic modality for resistant oral lichen planus. 8-isoprostane is a biomarker of lipid peroxidation that can be reduced by lycopene. Trial registration ID: PACTR202003484099670. 'Retrospectively registered on 11/3/2020'.