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Multidrug resistance protein 4 (MRP4) is a broadly expressed ATP-binding cassette transporter that is unique among the MRP subfamily for transporting prostanoids, a group of signaling molecules derived from unsaturated fatty acids. To better understand the basis of the substrate selectivity of MRP4, we used cryogenic-electron microscopy to determine six structures of nanodisc-reconstituted MRP4 at various stages throughout its transport cycle. Substrate-bound structures of MRP4 in complex with PGE1, PGE2 and the sulfonated-sterol DHEA-S reveal a common binding site that accommodates a diverse set of organic anions and suggest an allosteric mechanism for substrate-induced enhancement of MRP4 ATPase activity. Our structure of a catalytically compromised MRP4 mutant bound to ATP-Mg2+ is outward-occluded, a conformation previously unobserved in the MRP subfamily and consistent with an alternating-access transport mechanism. Our study provides insights into the endogenous function of this versatile efflux transporter and establishes a basis for MRP4-targeted drug design.

Background: Chronic inflammation and its control are crucial to the responses of glomerular and renal tubular cells. This contributes to the pathogenic mechanisms and advancement of the disease in Alport syndrome. The study aimed to elucidate the role of cyclooxygenase-2, Interleukin 4, Plasminogen activating inhibitor 1, and Prostaglandin E2 in the development and course of Alport syndrome. Methods: In our study inflammatory markers were evaluated in 26 Alport syndrome patients, 15 males and 11 females and 24 controls. Results: Their age ranged from 4 to 16 years (mean ± SD was 8.50 ± 2.877) and 24 were normal controls matching age and sex. The serum levels of cyclooxygenase-2, Prostaglandin E2, Interleukin 4, and Plasminogen activating inhibitor 1 were evaluated in all patients. The serum level of cyclooxygenase-2, Prostaglandin E2, Interleukin 4, and Plasminogen activating inhibitor 1 were all increased significantly in the Alport syndrome patients compared to control (588.68 ± 73.08, 42.57 ± 4.18, 42.32 ± 3.49, and 846.47 ± 45.433, respectively versus controls (369.12 ± 50.28, 25.52 ± 4.98, 28.89 ± 3.19, and 312.79 ± 40.53 respectively). Conclusion: The role of inflammatory markers cyclooxygenase-2, Prostaglandin E2, Interleukin 4, and Plasminogen activating inhibitor 1 in Alport syndrome that are causally connected and have a role in the development and course of Alport disease was delineated. This may highlight and speculate an innovative strategy for targeting the creation of safe and efficient anti-inflammatory treatments to inhibit disease progression in Alport syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Heracleum L. has been known as "hogweed" and used for inflammatory diseases, including fever, enteritis, and bronchitis, for many years worldwide. The Heracleum genus is also prominently recognized for its high content of coumarins, which are considered a significant group of natural compounds known for their noteworthy anti-inflammatory properties. Methods: The present study evaluated the anti-inflammatory activity of dichloromethane and methanolic extracts from H. paphlagonicum , H. sphondylium subsp. ternatum , H. sphondylium subsp. elegans , and H. sphondylium subsp. cyclocarpum (100 mg/kg), which have not been previously investigated for their anti-inflammatory properties. Inflammation models induced by carrageenan, prostaglandin E2, and serotonin were employed to evaluate anti-inflammatory activity, using indomethacin (10 mg/kg) as the reference standard. Statistical differences between treatment and control groups were evaluated using ANOVA with Student-Newman-Keuls post-hoc tests. Additionally, the coumarin contents of the extracts were quantified as mg/g by high-performance liquid chromatography. Results and discussion: H. sphondylium subsp. cyclocarpum roots displayed the highest inhibition for carrageenan, prostaglandin E2, and serotonin-induced hind paw edema, with inhibition ranges of 22.8%–36.9%, 5.4%–35.7%, and 3.9%–17.9%, respectively, while the inhibition ranges for indomethacin were 12.8%–44.3%, 2.7%–41.3%, and 7.1%–30.6%, respectively. The highest bergapten and imperatorin quantities were found in H. sphondylium subsp. cyclocarpum roots (0.49% and 0.14%) and in H. sphondylium subsp. elegans roots, which had the highest xanthotoxin level (0.06%). Angelicin was detected in H. paphlagonicum , H. sphondylium subsp. elegans , and H. sphondylium subsp. cyclocarpum roots at concentrations of 0.04%, 0.04%, and 0.02%, respectively. The correlation between the highest inhibitory activity observed in H. sphondylium subsp. cyclocarpum roots and the elevated levels of coumarins, particularly bergapten and imperatorin, suggests a potential link between coumarin concentration and anti-inflammatory effects. Additionally, our findings support the traditional use of this genus for treating inflammatory disorders. Further investigations are necessary to identify the active compounds and elucidate the mechanisms of action of these plants, potentially leading to the discovery of novel therapeutic options for the treatment of inflammation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Tumor-derived Prostaglandin E2 (via COX-2) and host gut-originated LPS synergistically amplify hypothalamic inflammation in vitro and in vivo. • Prostaglandin E2 directly induces hypothalamic inflammation through EP4 receptor activation. • Prostaglandin E2 enhances hypothalamic inflammation via NF-κB pathways in the presence of host gut-derived PAMPs. • Tumor-specific COX-2 knockout attenuates hypothalamic inflammation and improves survival during cancer. Hypothalamic inflammation often coincides with cancer and cachexia-anorexia. Prior work established the significance of tumor-derived inflammatory factors in triggering hypothalamic inflammation, yet the precise mechanisms remained elusive. Here, we demonstrate that prostaglandin E2 (PGE2), produced in the tumor via cyclooxygenase-2 (COX-2), plays a pivotal role in this context. PGE2 itself directly exerts pro-inflammatory effects on the hypothalamus through the EP4 receptor, while also augmenting hypothalamic inflammation via NF-κB pathways in the presence of host gut-derived pathogen-associated molecular patterns (PAMPs). In tumor-bearing mice, we confirm this synergistic interaction between tumor-derived COX-2/PGE2 and host-derived lipopolysaccharide (LPS) in amplifying hypothalamic inflammation. Supporting this mechanism we find that the tumor-specific knockout of COX-2 attenuates hypothalamic inflammation and improves survival in mice. Together, these findings highlight the mechanisms of tumor-associated COX-2 in fuelling hypothalamic inflammation. They also emphasize the potential of tumor-specific COX-2 inhibition and targeting gut permeability as a novel therapeutic strategy for improving clinical outcomes in cancer patients. [ABSTRACT FROM AUTHOR]

Background This study investigated the association between prostaglandins, vitamin D levels, and their potential role in acute myeloid leukemia (AML). Previous research has shown prostaglandins' stimulatory effects and vitamin D's inhibitory effects in various malignancies. Methods This cross-sectional study evaluated 54 AML patients at Shahid Ghazi Center of Imam Reza Hospital in Tabriz. Prostaglandin E2 (PGE2), Cyclooxygenase-2 (COX-2), and serum vitamin D levels, as well as gene expression of 5-hydroxyprostaglandin dehydrogenase (15-PGDH), COX-2, PGE2 synthase, and vitamin D receptor (VDR), were measured. Relationships were assessed between vitamin D levels, COX-2 and PGE2 expression, serum levels, and treatment outcomes. Results Median serum vitamin D level was 18.25 ng/mL (range: 4.00-72.70). There was no significant association between serum vitamin D levels and expression or serum levels of COX-2, PGE2 synthase, and 15-PGDH. VDR gene expression and serum levels showed significant direct correlations with PGE2 and COX-2 gene expression and serum concentrations and inverse correlations with 15-PGDH expression (P < 0.05). No statistically significant correlation was observed between vitamin D status, PGE2, COX-2, and 15-PGDH with treatment outcomes. Conclusion This study on AML patients showed no significant correlation between vitamin D levels and COX-2, PGE2 synthase, or 15-PGDH. VDR expression correlated positively with PGE2 and COX-2 but negatively with 15-PGDH. No associations were found between these factors and therapy outcomes. [ABSTRACT FROM AUTHOR]

The orientation and function of smooth muscle in the cervix may contribute to the important biomechanical properties that change during pregnancy. Thus, this study examined the three-dimensional structure, smooth muscle phenotype, and mechanical and contractile functions of the upper and lower cervix of nongravid (not pregnant) and gravid (pregnant) mice. In gravid cervix, we uncovered region-specific changes in the structure and organization of fiber tracts. We also detected a greater proportion of contractile smooth muscle cells (SMCs), but an equal proportion of synthetic SMCs, in the upper versus lower cervix. Furthermore, we revealed that the lower cervix had infrequent spontaneous contractions, distension had a minimal effect on contractility, and the upper cervix had forceful contractions in response to labor-inducing agents (oxytocin and prostaglandin E2). These findings identify regional differences in cervix contractility related to contractile SMC content and fiber organization, which could be targeted with diagnostic technologies and for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Objective: Our aim in this study was to compare the mode of delivery in pregnancies with fetal growth restriction(FGR) and with normal antenatal assesment udergoing induction of labor(IOL) with vaginal application of dinoprostone. Methods: This was a retrospective cohort study of consecutive pregnancies undergoing IOL with vaginal dinoprostone between 2022 to 2023 at our hospital. Participants with a prenatal diagnosis of FGR were compared with those without FGR. Results: We found that IOL with dinoprostone did not increase the cesarean section rate when compared with fetuses with FGR and APGAR scores at 1 and 5 minuted were similar in both groups. Conclusion: In conclusion, IOL with dinoprostone in fetuses with FGR seems to be as safe as for non-FGR fetuses. [ABSTRACT FROM AUTHOR]

Hydrogen-rich Gynostemma pentaphyllum Makino distillate (HRGD) is produced by distilling G. pentaphyllum Makino, with the addition of hydrogen gas. This study sought to explore the pharmacological and biological impacts of HRGD on the generation of pro-inflammatory cytokines and mediators in macrophages. The cells were treated with various concentrations of HRGD (2, 4 and 8 μg/mL) in the absence or presence of lipopolysaccharide (LPS) (1 μg/mL) for 24 h. The results indicated that HRGD is an effective inhibitor of LPS-induced nitric oxide (NO·) production in RAW 264.7 cells: The NO· concentration was reduced dramatically after treatment with 8 μg/m98L HRGD (11.8 μM) compared to the LPS-induced group (28.4 μM). These inhibitory effects of HRGD included a dose-dependent decrease in the expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) proteins. To evaluate the inhibitory effects of HRGD on other cytokines, we also measured cytokines tumor necrosis factor-α (TNF-α) level in the cell supernatants of LPS-stimulated RAW 264.7 macrophages by enzyme-linked immunosorbent assay. In this assay, HRGD significantly decreased the expression of TNF-α in a dose-dependent manner (p < 0.05). The study also performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on macrophages. HRGD did not display any cytotoxicity in this assay. The findings demonstrated that HRGD could modulate macrophage-mediated inflammatory functions such as the overproduction of cytokines, NO· and PGE2 without any cytotoxic. [ABSTRACT FROM AUTHOR]

Objective: To explore the complications and pregnancy outcomes of vaginal dinoprostone vs. Cook's double balloon for the induction of labor among pregnancies complicated by small-for-gestational-age (SGA) at term. Methods: This retrospective study included consecutive singleton pregnancies complicated by SGA treated at Fujian Maternity and Child Health Hospital between January 2017 and December 2021. The patients were divided into the Cook's double balloon and dinoprostone groups according to the induction method they received. The primary outcome was vaginal delivery. Results: This study included 318 women [165 (aged 30.25 ± 4.72 years) and 153 (aged 28.80 ± 3.91 years) in the dinoprostone and Cook's balloon groups]. The dinoprostone group had a higher vaginal delivery rate than the Cook's balloon group (83.6% vs. 71.9%, p =.012). The cervical ripening duration (9.73 ± 4.82 vs. 17.50 ± 8.77 h, p <.001) and induction to delivery duration (22.11 ± 8.13 vs. 30.27 ± 12.28, p <.001) were significantly shorter in the dinoprostone group compared with the Cook's balloon group. Less women needed oxytocin infusion in the dinoprostone group compared with that in the Cook's balloon group (32.7% vs. 86.3%, p <.001). Dinoprostone was independently associated with vaginal delivery (HR = 1.756, 95%CI: 1.286–2.399, p =.000). The rates of uterine tachysystole and spontaneous rupture of the fetal membrane were significantly higher in the dinoprostone group than that in the Cook's balloon group (10.3% vs. 0.7%, p <.001; 7.3% vs. 1.3%, p =.012). There were no differences in maternal complications and neonatal outcomes between the two groups. Conclusion: In pregnant woman with pregnancies complicated by SGA, cervical ripening using dinoprostone were more likely to achieve vaginal delivery than those with Cook's balloon, and with a favorable complication profile. [ABSTRACT FROM AUTHOR]

Oxylipin signalling is central in biology, mediating processes such as cellular homeostasis, inflammation and molecular signalling. It may also facilitate inter‐partner communication in the cnidarian‐dinoflagellate symbiosis, though this aspect remains understudied. In this study, four oxylipin receptors were characterised using immunohistochemistry and immunoblotting in the sea anemone Exaiptasia diaphana ('Aiptasia'): Prostaglandin E2 receptor 2 (EP2) and 4 (EP4), Transient Receptor Potential cation channel A1 (TRPA1) and Glutamate Receptor Ionotropic, Kainate 2 (GRIK2). Receptor abundance and localisation were compared between aposymbiotic anemones and symbiotic anemones hosting either native Breviolum minutum or non‐native Durusdinium trenchii. All receptors were localised to the putative symbiosome of freshly isolated symbionts, suggesting a role in host‐symbiont crosstalk. EP2, EP4 and TRPA1 abundance decreased in the gastrodermis of anemones hosting B. minutum, indicating potential downregulation of pathways mediated by these receptors. In contrast, GRIK2 abundance increased in anemones hosting D. trenchii in both the epidermis and gastrodermis; GRIK2 acts as a chemosensor of potential pathogens in other systems and could play a similar role here given D. trenchii's reputation as a sub‐optimal partner for Aiptasia. This study contributes to the understanding of oxylipin signalling in the cnidarian‐dinoflagellate symbiosis and supports further exploration of host‐symbiont molecular signalling. [ABSTRACT FROM AUTHOR]

Aim: The induction of labor before due date has recently been proved to reduce the rate of cesarean sections and is not associated with increased risk of adverse perinatal outcomes as compared to expectant management. Controlled‐release dinoprostone (PGE2) vaginal insert has recently been approved for use in Japan. However, evidence regarding its efficacy in cervical ripening and labor induction before due date remains limited. We aimed to compare the efficacy of PGE2 vaginal inserts and mechanical dilation for labor induction before due date. Methods: This retrospective cohort study included 206 mothers at 37, 38, and 39 weeks' gestation delivered at our institution between January 2021 and October 2022. Perinatal outcomes, including the success rate of vaginal delivery, were compared between the PGE2 (n = 46) and metreurynter/laminaria tent (non‐PGE2) (n = 160) groups. The success rate of vaginal delivery was defined as the proportion of women who delivered vaginally within 48 h of initiating oxytocin augmentation. Results: The success rate of vaginal delivery was significantly higher in the PGE2 group (37/49, 80.4%) than in the non‐PGE2 group (106/177, 66.2%). Emergency cesarean section related to non‐reassuring fetal status was performed with none in the PGE2 group and with eight (5.0%) in the non‐PGE2 group. Conclusions: The rate of vaginal delivery was significantly higher in the PGE2 group for elective labor induction between 37 and 39 weeks. The PGE2 vaginal insert could increase the success rate of vaginal delivery for elective induction of labor at 39 weeks. [ABSTRACT FROM AUTHOR]

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Incorporating antioxidants into cosmetics is the mainstay for developing new products to mitigate skin aging. However, identifying novel multifunctional antioxidant ingredients with additional relevant properties that block the skin hallmarks of aging is a very striking strategy. Many natural compounds, including xanthones, have demonstrated biologically notable properties. In particular, 1,2-dihydroxy-9H-xanthen-9-one (1,2-DHX) has inhibitory activity against skin enzymes, and metal-chelating and radical-scavenging activities. Therefore, 1,2-DHX is an attractive molecule for cosmetic purposes. With this goal in mind, the anti-inflammatory, antioxidant, and anti-allergic potentials of 1,2-DHX were investigated. 1,2-DHX demonstrated anti-inflammatory properties by inhibiting the synthesis of specific pro-inflammatory mediators, including interleukin-6 (IL-6) and prostaglandin E2 (PGE2), in human macrophages. This xanthone did not elicit sensitization reactions and did inhibit allergic reactions triggered by a strong skin allergen, suggesting its potential as an anti-allergic compound. 1,2-DHX also revealed mitochondrial antioxidant activity by mitigating rotenone-induced oxidative stress in macrophages by up to 40%. Overall, 1,2-DHX displayed a safety profile and noteworthy biological activities, highlighting its multifunctional profile as an active cosmetic ingredient with anti-inflammatory, antioxidant, and anti-allergic properties. [ABSTRACT FROM AUTHOR]

The lipid prostaglandin E2 (PGE2) mediates inflammatory pain by activating G protein-coupled receptors, including the prostaglandin E2 receptor 4 (EP4R). Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce nociception by inhibiting prostaglandin synthesis, however, the disruption of upstream prostanoid biosynthesis can lead to pleiotropic effects including gastrointestinal bleeding and cardiac complications. In contrast, by acting downstream, EP4R antagonists may act specifically as anti-inflammatory agents and, to date, no selective EP4R antagonists have been approved for human use. In this work, seeking to diversify EP4R antagonist scaffolds, we computationally dock over 400 million compounds against an EP4R crystal structure and experimentally validate 71 highly ranked, de novo synthesized molecules. Further, we show how structure-based optimization of initial docking hits identifies a potent and selective antagonist with 16 nanomolar potency. Finally, we demonstrate favorable pharmacokinetics for the discovered compound as well as anti-allodynic and anti-inflammatory activity in several preclinical pain models in mice.

Background: NSAID-induced gastropathy is a health burden that requires effective intervention. Among various prevention options, Gardenia jasminoides fruit extract (GJE) has demonstrated gastroprotective effects through anti-inflammatory pathways with a wide safety margin. However, the detailed molecular mechanisms of GJE regarding mucoprotective and anti-inflammatory effects remained to be explored. Therefore, we investigated the effects of GJE on NSAID-induced gastric injury in rats, focusing on the expression of the protective factors: prostaglandin E2 (PGE2) and mucin 5AC (MUC5AC), and the aggravating factors: inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB). Methods: Twenty-four male Sprague–Dawley rats were assigned to three experimental groups (n = 8/group): the control group, the NSAIDs group receiving indomethacin to induce gastric ulcers, and the NSAIDs with GJE pretreatment (NSAIDs + GJE) group. After a two-day experimental period, the stomachs were collected for histopathological examination, immunohistochemical staining, and protein expression analysis in gastric tissue lysates. Results: The NSAIDs group exhibited severe neutrophil infiltration with ulcers upon gastric histopathological examination. Pretreatment with GJE attenuated NSAID-induced gastropathy, as evidenced by reduced neutrophil infiltration and decreased ulceration. Immunohistochemical staining and Western blotting demonstrated reduced expressions of PGE2 and MUC5AC, while the expressions of iNOS and NF-κB were increased following NSAID administration. In comparison to the NSAIDs group, the NSAIDs + GJE group exhibited higher expressions of PGE2 and MUC5AC and lower expressions of iNOS and NF-κB, providing evidence of the gastroprotective effects of GJE. Conclusions: Pretreatment with GJE alleviated NSAID-induced gastric ulcers by increasing the expression of PGE2 and MUC5AC and decreasing the expression of iNOS and NF-κB. This study contributes to the understanding of the mechanisms by which GJE attenuates NSAID-induced gastropathy. Further studies are required to validate the effect of GJE in clinical settings. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Materials and Methods Results Conclusion To analyse whether some selected inflammatory biomarkers collected from venous blood and gingival crevicular fluid (GCF) were associated with the outcome of non‐surgical periodontal therapy.Two‐hundred and nine patients affected by periodontitis were enrolled in the study, who had undergone steps I and II therapy as well as a non‐surgical re‐instrumentation (NSRI) of periodontal pockets after 6 months. Serum (SE), plasma (PL) and GCF samples were quantitatively analysed for the following inflammatory biomarkers: active matrix metalloproteinase‐8 (aMMP‐8), prostaglandin E2 (PGE2) and surfactant protein D (SP‐D). Therapy outcomes were evaluated using a ‘treat‐to‐target’ endpoint (T2T) at the patient level, defined as ≤ 4 sites with pocket depth ≥ 5 mm.Patients presented with 23 ± 6 teeth (mean ± SD) at baseline. After steps I and II therapy, 41.6% of the patients reached T2T and after NSRI 47.4%. Univariate analysis identified a potential association between high levels of PL‐SP‐D and more favourable treatment outcomes. Multivariate binary logistic regression adjusted for sex, mean baseline probing depth, diabetes and current smoking status confirmed an independent relationship between baseline PL‐SP‐D and the T2T after steps I and II therapy (aOR 0.432, p = 0.011), implying that a higher level PL‐SP‐D at baseline is associated with a > 50% reduced risk of failing T2T. However, no such association was found for PL‐SP‐D and NSRI.Higher baseline PL‐SP‐D levels might be associated with more favourable treatment outcomes after steps I and II therapy. This may be due to its role in the regulation of neutrophil function. However, further investigation is required to confirm this hypothesis. If proven, PL‐SP‐D could play a role as a biomarker for identifying individuals who respond differentially to primary therapy. [ABSTRACT FROM AUTHOR]

Objective Materials and Methods Results Conclusion This retrospective study aimed to compare the outcomes of dinoprostone vaginal insert (PROPESS) and double balloon cook catheter (DBC) in term nulliparous pregnancies.A total of 1682 cases were enrolled, all of which were divided into two groups: PROPESS and DBC. The primary outcomes were rate of vaginal delivery (VD) and cesarean section (CS) and successful VD within 24 h and CS indications; the secondary outcomes were labor duration, oxytocin augmentation, complications during labor, maternal/neonatal outcomes, and predictors of successful VD within 24 h.There was no statistical difference in the rates of VD between the PROPESS group (73.74%) and the DBC group (77.73%) (p = 0.36). The VD rate within 24 h was significantly higher in PROPESS group than in the DBC group (55.45% vs. 38.43%, p < 0.001). The occurrence of nonreassuring fetal heart rate (NRFHR) patterns was higher in the CS indications of the PROPESS group than in the DBC group (56.86% vs. 37.81%, p < 0.001). The oxytocin augmentation was significantly lower in the PROPESS group than in the DBC group (52.79% vs. 94.9%, p < 0.001). The incidence of chorioamnionitis was significantly higher in the DBC group as compared with PROPESS group (4.36% vs. 1.34%, p < 0.001), while neonatal outcomes were comparable between the two groups. PROPESS (p < 0.001, odds ratio [OR] 2.478, 95% confidence interval [CI] 1.718–3.574), oxytocin augmentation (p < 0.001, OR 32.759, 95% CI 20.654–51.958), and amniotomy (p = 0.016, OR 1.897, 95% CI 1.331–2.704) were predictors of VD within 24 h.The effectiveness of delivery was comparable between the two groups. The PROPESS group resulted in a high successful VD rate within 24 h, although accompanied by NRFHR occurrence. Two cases with fetal presentation change (cephalic to breech) and four cases with umbilical cord prolapse were observed in the DBC group. PROPESS, oxytocin augmentation, and amniotomy were associated with VD interval within 24 h. [ABSTRACT FROM AUTHOR]

Introduction: Labor induction exhibits considerable variations in protocols and medication regimens. Limited studies compare vaginal dinoprostone inserts with different oral misoprostol dosages, considering parity influence. This study explores the distinctions among 10 mg vaginal dinoprostone inserts and oral misoprostol 25 μg every 2 and every 4 h for labor induction, stratified by parity. Material and Methods: This retrospective cohort study involved 607 participants across two hospitals. The primary outcome, time from induction to delivery, and secondary outcomes, including mode of delivery and maternal and fetal safety, were assessed. Results: Patient characteristics revealed differences in indication for labor induction, with the dinoprostone cohort having fewer post‐term and premature rupture of membranes cases but more intrauterine growth restriction/small‐for‐gestational age. Both oral misoprostol regimens showed a shorter time to delivery interval compared to the dinoprostone cohort (median: 1380 min [IQR 1381.0] and 1127.0 min [IQR 1214.0] vs 1631.5 [IQR 1736.2], p < 0.001 and p = 0.014). Only the difference between oral misoprostol q2h and vaginal dinoprostone remained significant for nulliparous but not multiparous women, losing significance over all the population after adjusting for confounding factors. The proportion of women giving birth within 24 h did not significantly differ between misoprostol q2h and dinoprostone after adjusting for confounders. When comparing misoprostol q4h with dinoprostone after confounder adjustment, an increased time to delivery interval for misoprostol q4h was found (p = 0.001). Both oral misoprostol regimens exhibited fewer meconium‐stained liquor (miso q4h: OR 0.44, miso q2h: OR 0.34) and cesarean sections (miso q4h: OR 0.48, miso q2h: OR 0.53) compared to dinoprostone, even after adjustment for confounders. Conclusions: Our study suggests that oral misoprostol 25 μg q4h is less effective than 10 mg vaginal dinoprostone for labor induction if parity and indication for induction are adjusted for, particularly in multiparous women. In terms of side effects, oral misoprostol regimens seem superior to vaginal dinoprostone. Our data support the individualized use of different agents for labor induction according to parity, indication for induction, bishop score, and women's preference. [ABSTRACT FROM AUTHOR]

• Limited evidence on best strategy with unfavorable cervix 24 h after first vaginal dinoprostone. • Efficacy, maternal and neonatal morbidity after repeated methods questioned. • Similar vaginal delivery and neonatal morbidity between vaginal dinoprostone and cervical ripening balloon. • Cervical ripening balloon more efficient with more favourable cervix or labor within 24 h. To compare dinoprostone vaginal insert (PG) with cervical ripening balloon (CRB) as second line of cervical ripening in women at term with a persistent unfavorable cervix after first PG. This retrospective cohort study comprised all women with singleton fetus in cephalic presentation who required cervical ripening at term (≥37 weeks) for maternal and/or fetal disease using repeated PG or CRB for a persistent unfavorable cervix (Bishop score <6) 24 h after first PG. Primary outcome was vaginal delivery rate. Secondary outcomes were favorable cervix (Bishop score ≥6) or labor within 24 h after second device placement, postpartum hemorrhage (PPH) and neonatal morbidity. 180 women were analyzed (127 repeated PG (70.6 %) and 53 CRB after first PG (29.4 %)). After second device, 93.3 % of women had a favorable cervix (Bishop score ≥6) or were in labor within 24 h, and the rate was significantly higher after CRB, compared to repeated PG (98.1 % vs. 91.3 %; p = 0.048). Vaginal deliveries were similar between groups (62.2 % after repeated PG vs. 54.7 % after CRB; p = 0.36). PPH was observed in 22.2 % of included women, and no difference was observed between groups (21.3 % vs. 21.4 %; p = 0.63). Neonatal morbidity was similar between groups (13.4 % vs. 9.4 %; p = 0.48). Vaginal delivery rate and neonatal morbidity were similar when using PG or CRB as second line in women at term with a persistent unfavorable cervix after first PG. CRB seemed to be more efficient on the cervix status, compared to repeated PG, in these women. [ABSTRACT FROM AUTHOR]

Prostaglandin E2 (PGE2), an arachidonic acid metabolite, is a biologically active lipid small molecule, which was known as an inflammatory mediator previously. Macrophages are important cellular component of intrinsic immune system and the first line of defense against pathogenic invasion. Macrophages are highly plastic and can be simply divided into classically activated Ml type and alternative activated M2 type depending on their morphology and function. In healthy state, these two phenotypes of macrophages are in a dynamic balance to maintain immune homeostasis; when body is stimulated by infection or inflammation, M1/M2 can be converted to each other, thus participating in disease onset and progression and influencing disease regression. It has been shown that PGE2 can regulate macrophage polarization in inflammatory diseases, involving complex mechanisms such as signaling pathways, metabolic processes, and miRNA regulatory networks. Therefore, this paper will briefly summarize mechanism of PGE2 regulation of macrophage polarization and effects of this regulation in inflammatory diseases. [ABSTRACT FROM AUTHOR]

Predicting the success of vaginal delivery is an important issue in preventing adverse maternal and neonatal outcomes. This study sought to examine whether measurement of the angle of progression (AoP) can predict a successful vaginal delivery following induction of labour (IoL) among late term nulliparous women with a low (4>) Bishop score. This prospective study included consecutive nulliparous pregnant women whose gestational age was 41 weeks and 1–6 days (late-term). The AoP was measured at least three times and their means were calculated. During the study period, data of 150 women were included in the final analysis. Thirty-eight women underwent CS due to failure to progress (n=30) or NRGHR (n=8), while the remaining 112 women underwent NVD, with four women requiring vacuum extraction. The two groups were similar with respect to age, gestational age, BMI, estimated foetal weight, and birth weight. Women undergoing NVD differed significantly from those undergoing CS with respect to a greater ultrasonographic AoP (113.8±11.9° vs. 98.1±10.9°, p=0.0001), a shorter duration of dinoprostone use, shorter time to labour contraction, and a shorter duration of labour. In ROC analysis, the cut-off value for AoP was 100° for the prediction of successful IoL for NVD, with a sensitivity of 96 % and a specificity of 63 %. AoP may be a useful sonographic parameter for predicting successful vaginal delivery among nulliparous women at late term undergoing IoL; an AOP wider than 100° is associated with a high rate of vaginal delivery. [ABSTRACT FROM AUTHOR]

Background/Aim: As prostaglandin E2 (PGE2) and its receptors (EP2) are over-expressed on tumor cells and microenvironment, radiolabeled cyclodextrins targeting such biomolecules are valuable vector candidates in molecular cancer diagnostics. Using experimental melanoma models, we evaluated the in vivo imaging behavior of novel Manganese-52-labeled (52Mn) randomly methylated beta-cyclodextrin ([52Mn]Mn-DOTA-GA-RAMEB) and compared it with the following well-established tumor-specific probes: melanocortin-1 receptor (MC1-R)-affine [68Ga]Ga-DOTANAPamide and PGE2 selective [68Ga]Ga-DOTA-GA-RAMEB cyclodextrin. Materials and Methods: Post-injection of [68Ga]Ga-DOTA-NAPamide, [68Ga]Ga-DOTAGA-RAMEB, and [52Mn]Mn-DOTAGA-RAMEB into MC1-R positive B16F10 melanoma-bearing mice, tumor radio-pharmaceutical uptake was quantified in vivo and ex vivo using preclinical positron emission tomography (PET) and high-performance gamma counter. Results: Although all tracers performed well in tumor identification, the highest standardized uptake values were detected in the [68Ga]Ga-DOTA-NAPamide scans. Corresponding to the ex vivo data, meaningful [52Mn]Mn-DOTAGA-RAMEB accumulation 1 h post-injection confirmed the tumor-targeting potential of the tracer. Temporal changes in PGE2/EP2 expression of the neoplasms may explain the significant differences observed between the tumor uptake of the two cyclodextrin probes and that of the 52Mn-labelled compound measured 1 h, 4 h, and 3 days post-injection (p≤0.01, p≤0.05). Conclusion: Although further pharmacokinetical optimization may be required, 52Mn-labelled cyclodextrin holds potential in melanoma diagnostics and the PET-based longitudinal assessment of tumor-associated PGE2/EP2 expression. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that mesenchymal stem cells (MSCs) are safe for treating different tendinopathies. Synovial fluid is a pooled environment of biomarkers from the inflammatory and degenerative joint cavity. Understanding the effects of synovial fluid on MSCs is important, as it is the first microenvironment that administered MSCs encounter. Several studies have reported that exposure to osteoarthritic synovial fluid–activated MSCs increased the release of soluble factors; however, the paracrine effects of shoulder synovial fluid–stimulated umbilical cord-derived MSCs (SF-UC-MSCs) on tendinopathy have yet to be investigated. Purpose: To assess the effects of the conditioned media from SF-UC-MSCs on tenocytes from degenerative rotator cuff tears in an interleukin-1β (IL-1β)–induced tendinopathic condition. Study Design: Controlled laboratory study. Methods: UC-MSCs were isolated and cultured from healthy, full-term deliveries by cesarean section. Tenocytes were isolated and cultured from patients with degenerative rotator cuff tears. Conditioned media were obtained from UC-MSCs stimulated with synovial fluid. To evaluate the gene expression of proinflammatory and anti-inflammatory cytokines, enzymes and their inhibitors, matrix molecules, and growth factors, the tenocytes were cultured with IL-1β and 50% of the conditioned media from the SF-UC-MSCs; quantitative, real-time, reverse transcriptase polymerase chain reaction was also performed. A prostaglandin E2 (PGE2) assay was performed to investigate the PGE2 level secreted by the tenocytes. Western blotting was performed to examine protein synthesis of collagen type I and III. Cell viability, senescence, and apoptosis assays were also performed. Results: The conditioned media from the SF-UC-MSCs interfered with the inflammatory gene expression on tenocytes induced by IL-1β, but it increased the gene expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-3. Meanwhile, the conditioned media decreased the PGE2 level on cells induced by IL-1β. It did increase the type I/III ratio of gene expression and protein synthesis, mainly through the induction of type I collagen. Conditioned media of SF-UC-MSCs reversed senescence and apoptosis induced by IL-1β. Conclusion: Study findings indicated that the conditioned media from SF-UC-MSCs had anti-inflammatory effects and cytoprotective effects on IL-1β–treated tenocytes from degenerative rotator cuff tears. Clinical Relevance: UC-MSCs have useful potential for the treatment of tendinopathy in practice. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Methods Results Conclusion To compare and evaluate the differences between EGCG and phosphatidylcholine‐encapsulated EGCG in terms of their anti‐inflammatory and antioxidant capacities.In this study, transdermal absorption experiments were conducted to compare the absorption capacity of EGCG and phosphatidylcholine‐encapsulated EGCG. Subsequently, the disparity in anti‐inflammatory and antioxidant efficacy between EGCG and phosphatidylcholine‐encapsulated EGCG were evaluated through cytotoxicity experiments, as well as the determination of cellular inflammatory factors and the measurement of ROS content under different treatment conditions.The concentration of EGCG, encapsulated in phosphatidylcholine, in porcine skin is 40.76 ± 1.29 μg/cm2, which is significantly higher than the concentration of EGCG alone (31.62 ± 2.01 μg/cm2). Also, the ability of phosphatidylcholine‐encapsulated EGCG to suppress inflammatory factors such as tumor necrosis factor‐α (TNF‐α), cyclooxygenase‐2 (COX‐2), and prostaglandin E2 (PGE2) was notably superior to that of EGCG alone. Both phosphatidylcholine‐encapsulated EGCG and EGCG showed excellent ROS scavenging ability in terms of antioxidant capacity.The percutaneous absorption and anti‐inflammatory impact of EGCG encapsulated within phosphatidylcholine were substantially enhanced when compared to EGCG by itself. Additionally, both formulations exhibited enhanced ROS scavenging capacities, albeit the variance between them was not pronounced. These insights furnish a vital theoretical underpinning for the utilization of phosphatidylcholine‐encapsulated EGCG in cosmetic applications, specifically for fostering products with anti‐inflammatory and antioxidant benefits. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To assess adverse obstetric and neonatal outcomes associated with the use of dinoprostone for induction of labor, with particular attention on categories for which caution is recommended by the Italian Medicines Agency and the European Medicine Agency.A retrospective multicenter observational study was conducted on a population of 1687 patients undergoing induction of labor with vaginal dinoprostone (gel or insert) between August 2019 and June 2022. Patients were subdivided based on maternal age, gestational age, and obstetric disorders. Data regarding the mode of delivery, the incidence of tachysystole, and the obstetric and perinatal outcomes were collected.The main adverse event associated with the use of dinoprostone was tachysystole. However, tachysystole was not associated with an increased risk of cesarean section (CS), neonatal intensive care (NICU) admission, low 1‐min Apgar, or umbilical cord acidosis. Maternal age greater than 35 years, gestational age greater than 40 weeks, and obstetric disorders were not associated with an increased rate of tachysystole, NICU admission, low 1‐ and 5‐min Apgar scores, and cord acidosis. The only associated adverse outcomes in those categories were postpartum hemorrhage with age greater than 35 years and tachysystole with gestational diabetes mellitus and hypertensive disorders. Not a single case of severe outcome (disseminated intravascular coagulation, uterine rupture, maternal and fetal death) was reported in the cohort.Providing there is adequate maternal and fetal surveillance, in an inpatient setting, dinoprostone could be safely administered for the induction of labor and considered appropriate in high‐risk pregnancies. Tachysystole can be self‐identified by the patient and effectively managed. [ABSTRACT FROM AUTHOR]

Objective: Postdate pregnancies, defined as pregnancies that extend beyond the 40th-week gestation, are associated with an increased risk of adverse maternal and fetal outcomes. Consequently, there is a clinical need to manage these pregnancies effectively to prevent complications. Two common methods for inducing postdate pregnancies are the use of Foley catheters and prostaglandins. To determine the success rates of the Foley catheter and prostaglandin E2 (PGE2) in females with postdate pregnancy. Methods: 162 female participants were randomly divided into two groups through the lottery method. Group A utilised a Foley catheter, where after speculum examination, a 16F standard Foley catheter was aseptically inserted above the internal cervical os and inflated with 30ml of sterile water. In Group B, PGE 2 gel was administered, with nulliparous women receiving an initial dose of 2 mg per vaginum (PV) and parous women receiving 1mg PV. The gel was inserted into the posterior vaginal fornix. Success was defined as female giving within 24 hours. The data was analyzed using SPSS version 25. Results: The mean age of patients was 30.35 ± 6.89 years. Success was observed in 87(53.7%) patients, while 75(46.2%) patients did not achieve success. The study findings revealed that success was attained by 30(34.4%) individuals in group A and 57(65.5%) in group B. A statistically significant difference was observed between groups regarding the success of patients. i.e., p-value (<0.05) Conclusion: A study concludes that Prostaglandin E2 (PGE2) showed significantly higher success rates for achieving vaginal delivery within 24.0 hours when compared to Foley catheters in female individuals with postdate pregnancies. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to evaluate low‐dose oral misoprostol induction, and compare different methods used in second‐line induction in patients with a Bishop score less than 6. Methods: This retrospective study analyzed the medical history and courses of pregnancy of all patients induced with first‐line of low‐dose oral misoprostol (50 μg every 4 h with a total of 200 μg/24 h) from April 2021 to June 2022 in a university hospital center, and reported outcomes according to the second‐line method of induction. Results: Among 437 labor inductions with low‐dose oral misoprostol, 120 patients required a second‐line induction. Predictive factors of first‐line failure were higher body mass index (P = 0.011), absence of premature rupture of membranes (P = 0.021) and earlier term of pregnancy (P < 0.001). Regarding second methods of induction of labor, time from induction to delivery was shorter in the oxytocin group than the dinoprostone and misoprostol groups (24.0 vs. 41 and 51.0 h, respectively; P < 0.001), and was also significantly shorter in the dinoprostone than the misoprostol group (P = 0.048). Cesarean section rates did not differ between the three groups (P = 0.651). There were no clinically significant differences in adverse events between the groups. Conclusion: Normal body mass index, previous rupture of membranes and later term of induction of labor were the three favoring success factors during first‐line oral misoprostol. In cases of a Bishop score <6, oxytocin may be the best option to reduce duration to delivery, with the same maternal‐fetal outcomes, including a similar rate of vaginal delivery. Synopsis: If a Bishop score was <6 after 24 h oral misoprostol, oxytocin could be the best method to reduce duration to delivery. [ABSTRACT FROM AUTHOR]

Novel benzophenone–thiazole hybrids with different substituents were synthesized and evaluated for anti‐inflammatory activity using an ex vivo human whole‐blood assay. All hybrids (3c and 5a–h) showed significant anti‐inflammatory activity via prostaglandin E2 (PGE2) release inhibition. Moreover, 5c (82.8% of PGE2 inhibition), 5e (83.1% of PGE2 inhibition), and 5h (82.1% of PGE2 inhibition) were comparable to the reference drugs. Molecular docking revealed potential preferable binding to the active sites of cyclooxygenase 2 (COX‐2) and microsomal prostaglandin E synthase‐1 (mPGES‐1) enzymes. This study provides the first evidence that benzophenone–thiazole hybrids may also dock in mPGES‐1, a new attractive anti‐inflammatory drug target, besides providing promising ex vivo anti‐inflammatory activity. Thus, the novel hybrids are promising anti‐inflammatory lead compounds and highlight the significance of optimal substituent selection in the design of potent PGE2 inhibitors. [ABSTRACT FROM AUTHOR]

To compare effectiveness and safety of the Cook's balloon with vaginal dinoprostone to induce labor in patients with previous cesarean section. Observational, and retrospective study that included pregnant women at ≥ 37 weeks' gestation, with unfavorable cervix, singleton pregnancy, intact membranes, and a previous cesarean section, who had undergone labor induction in the period 2014–2019. 170 patients (86 balloon-84 dinoprostone) were analyzed. The proportion of women achieving vaginal delivery within 24 h was higher in the dinoprostone than in double-balloon group (RR, 3.24; 95% CI, 1.36–7.72). No significant differences were detected in the first 48 h in vaginal deliveries (P =.749) or in cesarean section rates (P =.634). Nor were there differences in maternal or fetal safety profiles. A body mass index > 35 increased the risk of cesarean section by 1.53 times (P =.017) and a Bishop's test score < 3 by 1.91 times (P =.009). A vaginal delivery following a cesarean section decreased the probability of another cesarean section by 0.46 times (P =.039). Labor induction with vaginal dinoprostone achieves better vaginal delivery rates in the first 24 h vs Cook's balloon. While the difference in uterine rupture rate did not reach significance, this was higher in women receiving prostaglandin. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that nuclear factor (NF)-κB is involved in the pathophysiology of mood disorders. Objectives and Methods: We conducted two experimental protocols in rats to investigate the effects of a selective NF-κB inhibitor (JSH-23) on (i) lipopolysaccharide (LPS)-induced inflammation and (ii) on behavioral phenotypes in rat models of depression (sucrose consumption test and forced swim test) and mania (amphetamine-induced hyperactivity test). Additionally, we tested the effects of JSH-23 on levels of inflammatory components (interleukin-6, prostaglandin E2, nuclear phospho-p65, and tumor necrosis factor-α) in the brain. Results: Acute treatment with JSH-23 (10 mg/kg, intraperitoneally [ip]) led to potent anti-inflammatory effects in LPS-treated rats, including a diminished hypothermic response to LPS and a reduction in pro-inflammatory mediators' levels in the brain. Chronic treatment with JSH-23 (3 mg/kg, ip, once daily, for 14 days) resulted in robust antidepressant-like effects (increased sucrose consumption and decreased immobility time). The antidepressant-like effects of JSH-23 were mostly accompanied by a reduction in levels of pro-inflammatory mediators in the brain. On the other hand, JSH-23 did not reduce amphetamine-induced hyperactivity. Conclusions: Altogether, these data suggest that NF-κB may be a potential therapeutic target for pharmacological interventions for depression. [ABSTRACT FROM AUTHOR]

Context Thiazide-induced hyponatremia is one of the most common forms of hyponatremia, but its pathogenesis is incompletely understood. Recent clinical data suggest links with prostaglandin E2 (PGE2) and a single nucleotide polymorphism (SNP) in the prostaglandin transporter gene (SLCO2A1), but it is unknown if these findings also apply to the general population. Objective To study the associations between serum sodium, thiazide diuretics, urinary excretions of PGE2, and its metabolite (PGEM), and the rs34550074 SNP in SLCO2A1 in the general population. Design Prospective population-based cohort study (Rotterdam Study). Setting General population. Participants 2178 participants (65% female, age 64 ± 8 years) Intervention(s) None. Main Outcome Measure(s) Serum sodium levels. Results Higher urinary PGE2 excretion was associated with lower serum sodium: difference in serum sodium for each 2-fold higher PGE2 −0.19 mmol/L [95% confidence interval (CI) −0.31 to −0.06], PGEM −0.29 mmol/L (95% CI −0.41 to −0.17). This association was stronger in thiazide users (per 2-fold higher PGE2 −0.73 vs −0.12 mmol/L and PGEM −0.6 vs −0.25 mmol/L, P for interaction <.05 for both). A propensity score matching analysis of thiazide vs non-thiazide users yielded similar results. The SNP rs34550074 was not associated with lower serum sodium or higher urinary PGE2 or PGEM excretion in thiazide or non-thiazide users. Conclusion Serum sodium is lower in people with higher urinary PGE2 and PGEM excretion, and this association is stronger in thiazide users. This suggests that PGE2-mediated water reabsorption regulates serum sodium, which is relevant for the pathogenesis of hyponatremia in general and thiazide-induced hyponatremia specifically. [ABSTRACT FROM AUTHOR]

Introduction. The physiological process by which the fetus and placenta are delivered from the uterus and pass through the vaginal canal for delivery is known as labor. Induction of labor involves deliberately initiating labor before it occurs naturally, using medical interventions or techniques to stimulate contractions and initiate the birthing process. Aim. This study aimed to investigate the factors that influence the success of labor induction procedures in Riyadh, Saudi Arabia, from January to April 2023. Subject and Methods. This retrospective chart review was conducted at the National Guard Hospital in Riyadh, Saudi Arabia. Data were collected from the patient chart of those who underwent labor induction from January to April 2023. The collected data were tabulated and cleaned in MS Excel. Final data were transferred to SPSS for subsequent data analysis. Results. Five hundred and thirty‐one pregnant women were analyzed. 52.7% were aged 30 years or below. The most common indication of IOL was post‐dated pregnancy (26.2%). 62% were normal deliveries, indicative of IOL success, while 31.1% were cesarean deliveries, indicative of IOL failure. In univariate analysis, women with lower gravidity (≤3) and who had received Propess were associated with cesarean delivery. In a multivariate regression analysis, women who received Prostin and increased parity were identified as the significant independent predictors of IOL success. Conclusion. IOL's success was dependent primarily on increasing parity and Prostin administration. However, lower gravidity (≤3) and Propess medication could lead to operative procedures among pregnant women. Hence, it is necessary to carefully assess the condition of pregnant women before directing them to IOL. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is one of the most prevalent malignancies affecting males; however, the role of inflammatory activity in the pathogenesis of this disease is not yet fully elucidated. Although inflammation is recognized as being closely associated with the onset and progression of PCa, the specific causal relationships between individual inflammatory factors and the disease require further clarification. Methods: Mendelian randomization (MR) methodologies can mitigate bias by utilizing whole-genome sequencing data, leveraging specific genetic variants to assess causal relationships between a given exposure and an outcome of interest. This research employed an MR approach to investigate the association between inflammatory cytokines and PCa. Results: In total, 44 inflammatory cytokines were evaluated in a large GWAS dataset to enable the drawing of robust conclusions. Elevated circulating Creactive protein (CRP) and prostaglandin E2 (PGE-2) levels were related to greater PCa risk. The reverse Mendelian randomization (MR) study indicates a causal relationship between prostate cancer and stem cell factor (SCF) (P=0.025). Conclusion: CRP and PGE-2 play crucial roles in the regulation of PCa development. Moreover, PCa may have an impact on SCF levels. Further research is imperative to elucidate whether these biomarkers can be effectively utilized to prevent or treat PCa. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify the roles of L-tryptophan (Trp) and its rate-limiting enzymes on the receptivity of bovine endometrial epithelial cells. Real-time PCR was conducted to analyze the differential expression of genes between different groups of bovine endometrial epithelial cells. Western blot was performed to detect Cyclooxygenase-2 (COX2) expression after treatment with Trp or kynurenine (the main metabolites of Trp). The kynurenine assay was used to examine if Trp or prostaglandin E2 (PGE2) can increase the production of kynurenine in the bovine endometrial epithelial cells. Results: Trp significantly stimulates insulin growth factor binding protein 1 (IGFBP1) expression, a common endometrial marker of conceptus elongation and uterus receptivity for ruminants. When bovine endometrial epithelial cells are treated with Trp, tryptophan hydroxylase-1 remains unchanged, but tryptophan 2,3-dioxygenase 2 (TDO2) is significantly increased, suggesting tryptophan is mainly metabolized through the kynurenine pathway. Kynurenine significantly stimulates IGFBP1 expression. Furthermore, Trp and kynurenine significantly increase the expression of aryl hydrocarbon receptor (AHR). CH223191, an AHR inhibitor, abrogates the induction of Trp and kynurenine on IGFBP1. PGE2 significantly induces the expression of TDO2, AHR, and IGFBP1. Conclusions: The regulation between Trp / kynurenine and PGE2 may be crucial for the receptivity of the bovine uterus. [ABSTRACT FROM AUTHOR]

Prostaglandin E2 (PGE2) has been reported to be involved in reproduction as one of the most abundant and widely distributed prostaglandins in invertebrates. Regulating gonad development and gamete production in mollusks can greatly assist artificial breeding, which is believed to promote the commercial benefits of various mollusk species. In the present study, the contents of PGE2 in the gonads of abalone at different developmental stages (maturing stage, ripe stage, and spawning stage) and reproduction states (before and after spawning) were measured. A higher PGE2 level was found in the gonads of abalones at the ripe stage than other stages, and the highest PGE2 level was detected in the ovaries of female H. diversicolor in the UV-stimulated group. Then the effects of PGE2 injection on the spawning efficiency were explored, and the gamete emission rates of female and male abalone were significantly increased after PGE2 injection. Through qRT-PCR and in situ hybridization assay, higher expression levels and wide distribution of phospholipase A2 (PLA2), cyclooxygenase 2 (COX2), prostaglandin E synthases (PGES2), and prostaglandin E2 receptor 4 (EP4) in the gonads of H. diversicolor were observed after spawning. It is speculated that PGE2 may promote the reproductive cycle in both male and female H. diversicolor, although the regulation mechanism of PGE2 in female and male abalone might be different. The results will be useful for the application of PGE2 in the abalone aquaculture practices to increase the reproduction efficiency in future. [ABSTRACT FROM AUTHOR]

Pulmonary surfactant serves as a barrier to respiratory epithelium but can also regulate airway smooth muscle (ASM) tone. Surfactant (SF) relaxes contracted ASM, similar to β2‐agonists, anticholinergics, nitric oxide, and prostanoids. The exact mechanism of surfactant relaxation and whether surfactant relaxes hyperresponsive ASM remains unknown. Based on previous research, relaxation requires an intact epithelium and prostanoid synthesis. We sought to examine the mechanisms by which surfactant causes ASM relaxation. Organ bath measurements of isometric tension of ASM of guinea pigs in response to exogenous surfactant revealed that surfactant reduces tension of healthy and hyperresponsive tracheal tissue. The relaxant effect of surfactant was reduced if prostanoid synthesis was inhibited and/or if prostaglandin E2‐related EP2 receptors were antagonized. Atomic force microscopy revealed that human ASM cells stiffen during contraction and soften during relaxation. Surfactant softened ASM cells, similarly to the known bronchodilator prostaglandin E2 (PGE2) and the cell softening was abolished when EP4 receptors for PGE2 were antagonized. Elevated levels of PGE2 were found in cultures of normal human bronchial epithelial cells exposed to pulmonary surfactant. We conclude that prostaglandin E2 and its EP2 and EP4 receptors are likely involved in the relaxant effect of pulmonary surfactant in airways. [ABSTRACT FROM AUTHOR]

Background: Irinotecan administration can lead to severe delayed-onset diarrhea (SDOD) in clinical practice. Currently, there is no reliable surrogate predictor of intestinal exposure to SN-38 and subsequent diarrhea incidence. Methods: The relationship between fecal 7-ethyl-10-hydroxycamptothecin (SN-38) content and SDOD was investigated in Fisher 344 rats using a novel spectrofluorimetric method. Additionally, a pharmacokinetic study of irinotecan was performed to evaluate the biodistribution of SN-38 to establish the relationship between tissue and fecal SN-38 exposure. Results: The spectrofluorimetric method was successfully employed to measure fecal SN-38 and CPT-11 content from Day 3 to Day 6 post-irinotecan administration. Only fecal SN-38 content on Day 3 exhibited a significantly positive correlation with SDOD incidence on Days 4 and 5. A cutoff value of SN-38 ≥ 0.066 mg/g in feces was identified, predicting severe diarrhea incidence with 81% accuracy and 80% specificity. The positive correlation between fecal SN-38 content and SN-38 exposure in the ileum on Day 3 was also reflected in the changes of indicators during intestinal injury, such as prostaglandin E2 level and antioxidant activity. Conclusion: Fecal SN-38 content proves to be representative of intestinal exposure to SN-38, indicative of intestinal injury, and predictive of SDOD incidence in rats, while the spectrofluorimetric method demonstrates the translational potential. Fecal SN-38 content as a surrogate predictor for SN-38 intestinal tissue exposure and irinotecan-induced severe delayed-onset diarrhea The intestinal SN-38 exposure, involving both the distribution of SN-38 from the blood vessel and the reabsorption of SN-38 from intestinal lumen, was shown to be closely related to irinotecan-induced diarrhea. However, intestinal SN-38 exposure is hard to measure in humans. Fecal SN-38 content could serve as a surrogate predictor of intestinal SN-38 exposure, which is dependent on biliary excretion, intestinal excretion to intestinal lumen and bacteria β-glucuronidase activities that convert SN-38G to SN-38. [ABSTRACT FROM AUTHOR]

Objective: To evaluate vaginal delivery in obese women who underwent cervical ripening at term using a dinoprostone vaginal insert or a cervical ripening balloon (CRB), and to assess maternal and neonatal morbidity according to the method. Methods: A prospective cohort study including obese women with a live singleton fetus in cephalic presentation who required cervical ripening at term (≥37 weeks) for maternal and/or fetal disease using a dinoprostone vaginal insert or a CRB. The primary outcome was vaginal delivery. Secondary outcomes were a favorable cervix (Bishop score >6) after 24 h, the time from device insertion to delivery, and composite maternal and neonatal morbidity. Results: In total, 135 consecutive women were analyzed (107 CRB, 79.3%; 28 dinoprostone vaginal insert, 20.7%). Vaginal delivery (86 [80.4%] after CRB vs 19 [67.9%] after dinoprostone vaginal insert; P = 0.248), favorable cervix within 24 h after device placement (52 [48.6%] vs 17 [60.7%]; P = 0.264), and maternal morbidity (12 [11.2%] vs 4 [14.3%]; P = 0.646) were similar between the groups. The time from device insertion to delivery also did not differ between the groups. Neonatal morbidity was significantly higher after the dinoprostone vaginal insert (11 [39.3%] vs 20 [18.7%]; P = 0.030). Cervical ripening using the dinoprostone vaginal insert, compared with the CRB, was significantly associated with neonatal morbidity (adjusted odds ratio 4.00, 95% confidence interval 1.34–12.5), but not with maternal morbidity (adjusted odds ratio 1.23, 95% confidence interval 0.30–4.38). Conclusions: Vaginal delivery, a favorable cervix after 24 h, the time from device insertion to delivery, and maternal morbidity did not significantly differ between the CRB and the dinoprostone vaginal insert for cervical ripening in obese women at term. Nevertheless, neonatal morbidity was significantly associated with the dinoprostone vaginal insert, compared with the CRB, among obese women who required cervical ripening at term. Synopsis: Neonatal morbidity was associated with vaginal dinoprostone, compared with a CRB, among obese women at term, without a difference in vaginal delivery and maternal morbidity. [ABSTRACT FROM AUTHOR]

There is controversial evidence that acidification of vaginal pH may increase the efficacy of vaginal prostaglandins in labor induction, with research being mainly focused on misoprostol. This study aims to evaluate the impact of this intervention on the progress of labor induction with dinoprostone (PGE2) vaginal tablet. This double-blind, parallel-group, randomized study was conducted between October 2021 and December 2022 at Alexandra General Hospital, Athens, Greece. A total of 230 women with singleton, full term pregnancy that were scheduled for labor induction were randomly divided into two groups: Group A, who received acidic vaginal wash (5 % acetic acid) and Group B, who received a normal saline vaginal wash. Afterwards, participants received a vaginal tablet of 3 mg dinoprostone every 6 h (maximum two doses). There were no statistically significant differences in mode of delivery, duration of different labor stages, Bishop score changes and possible complications. Participants in the acidification group needed less often labor augmentation with oxytocin and epidural anesthesia (p=0.03). Vaginal acidification seems to have no effect on the efficacy of the dinoprostone vaginal tablet. Even though it may reduce the need for oxytocin augmentation, there is no apparent benefit on clinical outcomes, such as reduction in cesarean section rates or shorter labor duration. Future research is necessary in order to validate these findings. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is a chronic multifactorial disease caused by microorganisms such as G-anaerobes in the periodontal tissues. It activates host defense cells and releases inflammatory mediators such as tumor necrosis factor-alpha (TNF-α) and prostaglandin E2 (PGE2). Ganoderma lucidum is a traditional medicinal mushroom with anti-inflammatory effects against various diseases. Biologically, different levels of its active constituents, such as triterpenoids and phenolic compounds, reduce inflammation with various pathways. Furthermore, the constituents inhibit toll-like receptor 4, MyD88 receptors, and the activities of nuclear factor-kappa B, which synthesize TNF-α and PGE2. Purpose: This study aimed to analyze the extent to which G. lucidum extract can reduce TNF-α and PGE2 levels in periodontitis model Sprague Dawley rats. Methods: Thirty Sprague Dawley rats were randomly divided into six groups of five rats. Periodontitis inflammation was induced by the injection of Porphyromonas gingivalis bacteria into intrasulcular gingival incisors in the lower jaw labial section. Grouping was as follows: Group K1 (healthy control); Group K2 (negative control); Group K3 (positive control with doxycycline dose 0.27 mg/kg BW); Group P1 (G. lucidum extract dose 5 mg/kg BW); Group P2 (G. lucidum extract dose 10 mg/kg BW); and Group P3 (G. lucidum extract dose 20 mg/kg BW). Samples were taken from rat gingival tissue and the levels of TNF-α and PGE2 were examined using the enzyme-linked immunosorbent assay method. Data analysis was performed using one-way analysis of variance (ANOVA) with a confidence level of 95% (p < 0.05). Results: The levels of TNF-α and PGE2 were the highest in the K2 group and the lowest in the K1 group. One-way ANOVA showed no significant difference in TNF-α and PGE2 levels between P3 and K1 group. Conclusion: G. lucidum extract can reduce TNF-α and PGE2 levels in Sprague Dawley rats with periodontitis. [ABSTRACT FROM AUTHOR]