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Background: Poor responders are those with poor ovarian reserve test, usually old age group however, there are some young patients with adequate ovarian reserve test are unexpectedly poorly responding to Controlled Ovarian Stimulation protocol ( COS) through In Vitro Fertilization (IVF) program. Follicular fluid and serum Prostaglandin D2 (PGD2) level has a role in ovarian function and response to COS protocol. Aim of study: To find whether follicular fluid and serum PGD2 level is a potential biomarker of ovarian reserve and a predictor of ovarian response to hyper stimulation and to show a possibility in developing a therapeutic factor for poor ovarian responders. Methods: The study included eighty infertile females less than 42 years old, their BMI less than 30 undergone Controlled Ovarian Stimulation (COS) protocol through IVF program. Forty of them with poor ovarian reserve (study group) defined according to ESHRE guidelines 2019; low Ati Mullerian hormones (AMH) and or low Antral Follicle Count (AFC), adding to them in my study Follicular Stimulating Hormone (FSH) level. Other forty with normal ovarian reserve test (control group). A third group extracted from control group, eight in number involving those with adequate ovarian reserve test and young age less than 35 years old, though showed unexpectedly poor response to COS protocol(total oocytes retrieved less than four). In our study we excluded women with endometriosis, immune disorder, endocrine disorders, women with endometriosis, women with polycystic ovarian syndrome and male factor infertility. We analysed PGD2 level using ELISA in both follicular fluid and patients serum on day of ovum pick up in both study group and control group, then we correlated the patients clinical parameters (age, BMI, ovarian reserve test),controlled ovarian stimulation / IVF program outcome (total oocytes retrieved, fertilisation rate and total embryos obtained) with follicular and serum PGD2 level. Finally we did comparison of all parameters mentioned above including follicular and serum PGD2 level among: (1) study group (poor ovarian reserve test) (2) new control group (normal ovarian reserve test and normal response with four oocytes retrieved and above) and (3) unexpected poorly responding group (normal ovarian reserve test, young less than 35 year and total oocytes retrieved less than four). Results: Showed significant lowered PGD2 level in both follicular fluid and patient's serum in study group (poor ovarian reserve group) in comparison with control group (normal reserve test). When we do the comparison among the three groups, the result showed significant lower follicular fluid PGD2 level, non-significant lower serum PGD2 level in unexpected poor responder group (age less than 35yr, normal ovarian reserve test, and poor response, less than four total oocytes retrieved) in comparison to group(normal ovarian reserve test and normal responder with equal or more than four total oocytes retrieved). There was no significant difference in follicular fluid and serum PGD2 level between study group (poor ovarian reserve test) and the unexpected poor responder group. Conclusion: We suggest that PGD2 is a potential biomarker to aid the tests of ovarian reserve and to enhance the diagnosis of poor ovarian response and this data may show the possibility of developing a therapeutic factor for poor ovarian responders by enhancing follicular function that can be used to establish new individualised COS protocol in women with poor ovarian response [ABSTRACT FROM AUTHOR]

Childbirth is a defining moment in anyone's life, and it occurs 140 million times per year. Largely a physiologic process, parturition does come with risks; one mother dies every two minutes. These deaths occur mostly among healthy women, and many are considered preventable. For each death, 20 to 30 mothers experience complications that compromise their short- and long-term health. The risk of birth extends to the newborn, and, in 2020, 2.4 million neonates died, 25% in the first day of life. Hence, intrapartum care is an important priority for society. The American Journal of Obstetrics & Gynecology has devoted two special Supplements in 2023 and 2024 to the clinical aspects of labor at term. This article describes the content of the Supplements and highlights new developments in the induction of labor (a comparison of methods, definition of failed induction, new pharmacologic agents), management of the second stage, the value of intrapartum sonography, new concepts on soft tissue dystocia, optimal care during the third stage, and common complications that account for maternal death, such as infection, hemorrhage, and uterine rupture. All articles are available to subscribers and non-subscribers and have supporting video content to enhance dissemination and improve intrapartum care. Our hope is that no mother suffers because of lack of information. [ABSTRACT FROM AUTHOR]

Oxytocin is a reproductive hormone implicated in the process of parturition and widely used during labor. Oxytocin is produced within the supraoptic nucleus and paraventricular nucleus of the hypothalamus and released from the posterior pituitary lobe into the circulation. Oxytocin is released in pulses with increasing frequency and amplitude in the first and second stages of labor, with a few pulses released in the third stage of labor. During labor, the fetus exerts pressure on the cervix of the uterus, which activates a feedforward reflex—the Ferguson reflex—which releases oxytocin. When myometrial contractions activate sympathetic nerves, it decreases oxytocin release. When oxytocin binds to specific myometrial oxytocin receptors, it induces myometrial contractions. High levels of circulating estrogen at term make the receptors more sensitive. In addition, oxytocin stimulates prostaglandin synthesis and release in the decidua and chorioamniotic membranes by activating a specific type of oxytocin receptor. Prostaglandins contribute to cervical ripening and uterine contractility in labor. The oxytocin system in the brain has been implicated in decreasing maternal levels of fear, pain, and stress, and oxytocin release and function during labor are stimulated by a social support. Moreover, studies suggest, but have not yet proven, that labor may be associated with long-term, behavioral and physiological adaptations in the mother and infant, possibly involving epigenetic modulation of oxytocin production and release and the oxytocin receptor. In addition, infusions of synthetic oxytocin are used to induce and augment labor. Oxytocin may be administered according to different dose regimens at increasing rates from 1 to 3 mIU/min to a maximal rate of 36 mIU/min at 15- to 40-minute intervals. The total amount of synthetic oxytocin given during labor can be 5 to 10 IU, but lower and higher amounts of oxytocin may also be given. High-dose infusions of oxytocin may shorten the duration of labor by up to 2 hours compared with no infusion of oxytocin; however, it does not lower the frequency of cesarean delivery. When synthetic oxytocin is administered, the plasma concentration of oxytocin increases in a dose-dependent way: at infusion rates of 20 to 30 mIU/min, plasma oxytocin concentration increases approximately 2- to 3-fold above the basal level. Synthetic oxytocin administered at recommended dose levels is not likely to cross the placenta or maternal blood-brain barrier. Synthetic oxytocin should be administered with caution as high levels may induce tachystole and uterine overstimulation, with potentially negative consequences for the fetus and possibly the mother. Of note, 5 to 10 IU of synthetic oxytocin is often routinely given as an intravenous or intramuscular bolus administration after delivery to induce uterine contractility, which, in turn, induces uterine separation of the placenta and prevents postpartum hemorrhage. Furthermore, it promotes the expulsion of the placenta. [ABSTRACT FROM AUTHOR]

This review assessed the efficacy and safety of pharmacologic agents (prostaglandins, oxytocin, mifepristone, hyaluronidase, and nitric oxide donors) and mechanical methods (single- and double-balloon catheters, laminaria, membrane stripping, and amniotomy) and those generally considered under the rubric of complementary medicine (castor oil, nipple stimulation, sexual intercourse, herbal medicine, and acupuncture). A substantial body of published reports, including 2 large network meta-analyses, support the safety and efficacy of misoprostol (PGE1) when used for cervical ripening and labor induction. Misoprostol administered vaginally at doses of 50 μg has the highest probability of achieving vaginal delivery within 24 hours. Regardless of dosing, route, and schedule of administration, when used for cervical ripening and labor induction, prostaglandin E2 seems to have similar efficacy in decreasing cesarean delivery rates. Globally, although oxytocin represents the most widely used pharmacologic agent for labor induction, its effectiveness is highly dependent on parity and cervical status. Oxytocin is more effective than expectant management in inducing labor, and the efficacy of oxytocin is enhanced when combined with amniotomy. However, prostaglandins administered vaginally or intracervically are more effective in inducing labor than oxytocin. A single 200-mg oral tablet of mifepristone seems to represent the lowest effective dose for cervical ripening. The bulk of the literature assessing relaxin suggests this agent has limited benefit when used for this indication. Although intracervical injection of hyaluronidase may cause cervical ripening, the need for intracervical administration has limited the use of this agent. Concerning the vaginal administration of nitric oxide donors, including isosorbide mononitrate, isosorbide, nitroglycerin, and sodium nitroprusside, the higher incidence of side effects with these agents has limited their use. A synthetic hygroscopic cervical dilator has been found to be effective for preinduction cervical ripening. Although a pharmacologic agent may be administered after the use of the synthetic hygroscopic dilator, in an attempt to reduce the interval to vaginal delivery, concomitant use of mechanical and pharmacologic methods is being explored. Combining the use of a single-balloon catheter with dinoprostone, misoprostol, or oxytocin enhances the efficacy of these pharmacologic agents in cervical ripening and labor induction. The efficacy of single- and double-balloon catheters in cervical ripening and labor induction seems similar. To date, the combination of misoprostol with an intracervical catheter seems to be the best approach when balancing delivery times with safety. Although complementary methods are occasionally used by patients, given the lack of data documenting their efficacy and safety, these methods are rarely used in hospital settings. [ABSTRACT FROM AUTHOR]

There is limited evidence on the association between the clinical course of patent ductus arteriosus (PDA) and prostaglandin (PG) metabolites. This study aimed to determine the influence of PDA treatment on urinary PG metabolite excretion in very-low-birth-weight (VLBW) infants. Urine samples were collected from 25 VLBW infants at 1, 3, and 7 days of age. Infants were separated into two groups: a PDA-treated group that received a cyclooxygenase-2 (COX) inhibitor (n = 12) and a control group that did not receive a COX inhibitor during the first 7 days after birth (n = 13). Urinary PG metabolite tetranor prostaglandin E 2 metabolite (t-PGEM) and tetranor prostaglandin D 2 metabolite (t-PGDM) levels were analyzed using liquid chromatography–tandem mass spectrometry. Urinary t-PGEM excretion levels were not significantly different between the groups at 1, 3, and 7 days of age. Urinary t-PGDM excretion levels at 1 day of age were higher in PDA-treated infants than in control infants (median [interquartile range]: 5.5 [2.6, 12.2] versus 2.1 [1.0, 3.9] ng/mg creatinine; p = 0.017); however, among PDA-treated infants, the levels were significantly lower at 3 and 7 days than at 1 day of age (5.5 [2.6, 12.2] versus 3.4 [1.7, 4.5] and 4.0 [1.7, 5.3] ng/mg creatinine, respectively; p < 0.05). The urinary t-PGDM excretion level in the control group did not significantly differ among the time points. PDA and COX inhibitor administration affected PG metabolism in VLBW infants. Our results indicated that urinary t-PGDM excretion was significantly associated with PDA-treatment in preterm infants. [ABSTRACT FROM AUTHOR]

Capsaicin induces the reversible opening of tight junctions (TJs) and enhances the delivery of hydrophilic macromolecules through a paracellular route. We previously revealed that TRPA1 is involved in the capsaicin-induced Ca2+ influx and TJ permeability increase, although there are no reports that capsaicin directly activates TRPA1. In this study, we investigated the upstream factors of TRPA1 using RNA-seq analysis, and found that the cyclooxygenase 2 (COX2) gene was upregulated by capsaicin. Cyclooxygenase 2 converts arachidonic acid (AA), a metabolite by phospholipase A2 (PLA2), to prostaglandins. Prostaglandin E2 (PGE2) production was stimulated by capsaicin, and capsaicin-induced Ca2+ influx was effectively inhibited by PLA2 and COX2 inhibitors. The AA-induced TJ permeability increase was inhibited by a TRPA1 antagonist, but the capsaicin- and AA-induced TJ permeability increases were hardly inhibited by a COX2 inhibitor. These results suggest that capsaicin-induced PLA2 activation and AA production are the important steps for the TJ permeability increase. [ABSTRACT FROM AUTHOR]

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Prostaglandin E 2 (PGE 2) exerts biological actions through its transport pathway involving intracellular synthesis, extracellular transport, and receptor binding. This study aimed to determine the localization of the components of the PGE 2 -transporting pathway in human dental pulp and explore the relevance of PGE 2 receptors (EP2/EP4) to angiogenesis and dentinogenesis. Protein localization of microsomal PGE 2 (mPGES)synthase, PGE 2 transporters (multidrug resistance-associated protein-4 [MRP4] and prostaglandin transporter [PGT]), and EP2/EP4 was analyzed using double immunofluorescence staining. Tooth slices from human third molars were cultured with or without butaprost (EP2 agonist) or rivenprost (EP4 agonist) for 1 week. Morphometric analysis of endothelial cell filopodia was performed to evaluate angiogenesis, and real-time polymerase chain reaction was performed to evaluate angiogenesis and odontoblast differentiation markers. MRP4 and PGT were colocalized with mPGES and EP2/EP4 in odontoblasts and endothelial cells. Furthermore, MRP4 was colocalized with mPGES and EP4 in human leukocyte antigen-DR-expressing dendritic cells. In the tooth slice culture, EP2/EP4 agonists induced significant increases in the number and length of filopodia and mRNA expression of angiogenesis markers (vascular endothelial growth factor and fibroblast growth factor-2) and odontoblast differentiation markers (dentin sialophosphoprotein and collagen type 1). PGE 2 -producing enzyme (mPGES), transporters (MRP4 and PGT), and PGE 2 -specific receptors (EP2/EP4) were immunolocalized in various cellular components of the human dental pulp. EP2/EP4 agonists promoted endothelial cell filopodia generation and upregulated angiogenesis- and odontoblast differentiation-related genes, suggesting that PGE 2 binding to EP2/EP4 is associated with angiogenic and dentinogenic responses. [ABSTRACT FROM AUTHOR]

Scleroderma is a rare, female predominant clinically heterogenous, autoimmune condition characterized by the presence of autoantibodies, vascular abnormalities, and fibrosis. Skin thickening as a result of fibrosis is a hallmark clinical finding, and the extent of this skin thickening further classifies clinical subsets of scleroderma. Organ systems affected may include pulmonary (interstitial lung disease, pulmonary arterial hypertension), renal (scleroderma renal crisis), gastrointestinal (dysmotility, reflux esophagitis, gastric antral vascular ectasia), cardiac (arrhythmias, cardiac fibrosis), and musculoskeletal (arthritis, contractures). Raynaud phenomenon and telangiectasis occur as a result of vascular involvement. Diagnostic workup requires a thorough history and physical examination, supplemented by autoantibody testing. No single therapeutic agent is indicated to treat all manifestations of scleroderma. Rather, system- or organ-based treatment is indicated. Not only are skin manifestations often the presenting feature of scleroderma, progressive skin changes carry prognostic implications, underscoring the value of dermatology insight for early diagnosis suspicion, referral to rheumatology, and timely management. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most typical type of joint disease. OA is distinguished by several characteristics, including synovitis (synovial membrane inflammation), progressive cartilage degradation, subchondral bone remodeling, and discomfort. Prostaglandin E2, which has been implicated in the regulation of inflammation and cartilage biology, is catabolized by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). This study is intended to evaluate the expression and function of 15-PGDH in cartilage. The expression of 15-PGDH mRNA and protein in cartilage was investigated using real-time reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblotting, and immunohistochemistry. IL-1 was applied to stimulate chondrocytes. Western blotting and real-time RT-PCR were utilized to measure 15-PGDH expression, and 18-Glycyrrhetinic acid was used to examine how 15-PGDH activity affected the expression of significant inflammatory and anabolic genes. 15-PGDH expression was lower in OA tissues compared to its expression in both healthy human and murine cartilage, suggesting that the reduced levels of 15-PGDH may contribute to OA development. Treatment with IL-1β downregulated 15-PGDH expression in human OA chondrocytes. We also showed that treatment with 18 βGA, an inhibitor of 15-PGDH activity, up-regulated the expression of key inflammatory genes, including iNOS, COX-2, and mPGES-1, and down-regulated the expression of the main anabolic genes, type II collagen and aggrecan, in cartilage. Together, these data suggest that 15-PGDH is involved in the pathogenesis of OA. They also suggest that targeting 15-PGDH expression and activity could be a new anti-OA therapy that specifically modulates PGE2 levels. [ABSTRACT FROM AUTHOR]

[Display omitted] • The disulfide bond order is analyzed. • Several detachments schemes for defining residue fragments are compared. • Fully quantum–mechanical MP2 calculations of a protein with 1102 residues are presented. • Protein-ligand binding is discussed for conventional residues in the fragment molecular orbital method. The disulfide bond order is analyzed in terms of localized molecular orbitals. Several schemes of fragment boundaries are proposed for defining fragments in proteins with sulfur bridges, and their accuracy is evaluated for the three-body expansion of the fragment molecular orbital method. Interactions of the ligand ibuprofen with residues in prostaglandin H(2) synthase-1 (PDB: 1EQG) are analyzed at the MP2 level. The role of sulfur bridges in the protein stability and ligand binding is discussed. [ABSTRACT FROM AUTHOR]

Introduction: Placental infection and inflammation are risk factors for adverse pregnancy outcomes, including preterm labor. However, the mechanisms underlying these outcomes are poorly understood.Methods: To study this response, we have employed a pregnant mouse model of placental infection caused by the bacterial pathogen Listeria monocyogenes, which infects the human placenta. Through in vivo bioluminescence imaging, we confirm the presence of placental infection and quantify relative infection levels. Infected and control placentas were collected on embryonic day 18 for RNA sequencing to evaluate gene expression signatures associated with infection by Listeria.Results: We identified an enrichment of genes associated with eicosanoid biosynthesis, suggesting an increase in eicosanoid production in infected tissues. Because of the known importance of eicosanoids in inflammation and timing of labor, we quantified eicosanoid levels in infected and uninfected placentas using semi-targeted mass spectrometry. We found a significant increase in the concentrations of several key eicosanoids: leukotriene B4, lipoxin A4, prostaglandin A2, prostaglandin D2, and eicosatrienoic acid.Discussion: Our study provides a likely explanation for dysregulation of the timing of labor following placental infection. Further, our results suggest potential biomarkers of placental pathology and targets for clinical intervention. [ABSTRACT FROM AUTHOR]

Cyclooxygenases play a vital role in inflammation and are responsible for the production of prostaglandins. Two cyclooxygenases are described, the constitutive cyclooxygenase-1 and the inducible cyclooxygenase-2, for which the target inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs). Prostaglandins are a class of lipid compounds that mediate acute and chronic inflammation. NSAIDs are the most frequent choices for treatment of inflammation. Nevertheless, currently used anti-inflammatory drugs have become associated with a variety of adverse effects which lead to diminished output even market withdrawal. Recently, more studies have been carried out on searching novel selective COX-2 inhibitors with safety profiles. In this review, we highlight the various structural classes of organic and natural scaffolds with efficient COX-2 inhibitory activity reported during 2011–2021. It will be valuable for pharmaceutical scientists to read up on the current chemicals to pave the way for subsequent research. As a crucial enzyme for catalyzing the synthesis of prostaglandins, cyclooxygenase-2 (COX-2) was identified as a promising target for inflammation treatment. This review highlights the current progress of developing COX-2 inhibitors with various synthetic and natural structures as NSAIDs candidates. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: POR (cytochrome P450 reductase) provides electrons for the catalytic activity of the CYP (cytochrome P450) monooxygenases. CYPs are dual-function enzymes as they generate protective vasoactive mediators derived from polyunsaturated fatty acids but also reactive oxygen species. It is not known in which conditions the endothelial POR/CYP system is beneficial versus deleterious. Here, the activity of all CYP enzymes was eliminated in the vascular endothelium to examine its impact on vascular function.Methods: An endothelial-specific, tamoxifen-inducible POR knockout mouse (ecPOR-/-) was generated. Vascular function was studied by organ chamber experiments. eNOS (endothelial nitric oxide synthase) activity was accessed by heavy arginine/citrulline LC-MS/MS detection and phosphorylation of serine1177 in aortic rings. CYP-derived epoxyeicosatrienoic acids and prostanoids were measured by LC-MS/MS. Gene expression of aorta and endothelial cells was profiled by RNA sequencing. Blood pressure was measured by telemetry.Results: Acetylcholine-induced endothelium-dependent relaxation was attenuated in isolated vessels of ecPOR-/- as compared with control mice. Additionally, ecPOR-/- mice had attenuated eNOS activity and eNOS/AKT phosphorylation. POR deletion reduced endothelial stores of CYP-derived epoxyeicosatrienoic acids but increased vascular prostanoids. This phenomenon was paralleled by the induction of genes implicated in eicosanoid generation. In response to Ang II (angiotensin II) infusion, blood pressure increased significantly more in ecPOR-/- mice. Importantly, the cyclooxygenase inhibitor Naproxen selectively lowered the Ang II-induced hypertension in ecPOR-/- mice.Conclusions: POR expression in endothelial cells maintains eNOS activity and its loss results in an overactivation of the vasoconstrictor prostanoid system. Through these mechanisms, loss of endothelial POR induces vascular dysfunction and hypertension. [ABSTRACT FROM AUTHOR]

Background: Vascular smooth muscle cell (VSMC) phenotype transition plays an essential role in vascular remodeling. PGD2 (Prostaglandin D2) is involved in cardiovascular inflammation. In this study, we aimed to investigates the role of DP1 (PGD2 receptor 1) on VSMC phenotype transition in vascular remodeling after Ang II (angiotensin II) infusion in mice.Methods: VSMC-specific DP1 knockout mice and DP1flox/flox mice were infused with Ang II for 28 days and systolic blood pressure was measured by noninvasive tail-cuff system. The arterial samples were applied to an unbiased proteome analysis. DP1f/f Myh11 (myosin heavy chain 11) CREERT2 R26mTmG/+ mice were generated for VSMC lineage tracing. Multiple genetic and pharmacological approaches were used to investigate DP1-mediated signaling in phenotypic transition of VSMCs in response to Ang II administration.Results: DP1 knockout promoted vascular media thickness and increased systolic blood pressure after Ang II infusion by impairing Epac (exchange protein directly activated by cAMP)-1-mediated Rap-1 (Ras-related protein 1) activation. The DP1 agonist facilitated the interaction of myocardin-related transcription factor A and G-actin, which subsequently inhibited the VSMC transition to myofibroblasts through the suppression of RhoA (Ras homolog family member A)/ROCK-1 (Rho associated coiled-coil containing protein kinase 1) activity. Moreover, Epac-1 overexpression by lentivirus blocked the progression of vascular fibrosis in DP1 deficient mice in response to Ang II infusion.Conclusions: Our finding revealed a protective role of DP1 in VSMC switch to myofibroblasts by impairing the phosphorylation of MRTF (myocardin-related transcription factor)-A by ROCK-1 through Epac-1/Rap-1/RhoA pathway and thus inhibited the expression of collagen I, fibronectin, ED-A (extra domain A) fibronectin, and vinculin. Thus, DP1 activation has therapeutic potential for vascular fibrosis in hypertension. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most common form of musculoskeletal disease and a major cause of long-term disability with a significant socioeconomic impact. The primary clinical signs of OA include joint pain, stiffness, and a restricted range of motion. Age, obesity, joint damage, poor knee alignment, and genetics are identified as risk factors for OA, and the main pathological characteristics of OA include the cartilage progressive degeneration, synovium inflammation, and subchondral bone sclerosis. The prostaglandin D2 receptor, D prostanoid receptor 1 (DP1), is essential for modulating inflammation and cartilage metabolism. Our previous findings demonstrated that DP1 signalling is protective against OA in mice and down-regulates catabolic responses in cultured chondrocytes. Nonetheless, little is known about the DP1 transcriptional regulation mechanisms in cartilage The aim of this study was to characterize the human DP1 promoter and investigate how DNA methylation affects DP1 expression in chondrocytes. Furthermore, we assessed the methylation state and expression level of the DP1 gene promoter in both normal and OA cartilage. A minimal promoter region (-250/-120) containing three binding sites for specificity protein 1 (Sp1) was identified by deletion and site-directed mutagenesis analyses. Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) were used to confirm the binding of Sp1 to the DP1 promoter. Both DP1 mRNA expression and DP1 promoter activity were reduced by treatment with the Sp1 inhibitor mithramycin A. Treatment with DNA methylation inhibitor, 5-Aza-2′-deoxycytidine, up-regulated DP1 expression, and the DP1 promoter activity was reduced in the in vitro methylation. There was no difference in the methylation status of the DP1 promoter or the level of DP1 expression between normal and OA cartilage Our findings suggest that DNA methylation and the transcription factor Sp1 are important determinants of DP1 transcription regulation. Furthermore, they suggest that OA cartilage does not exhibit changes in the methylation status or expression level of DP1. These results will advance our knowledge of the DP1 transcription regulatory mechanisms and could help design DP1-related intervention tactics. [ABSTRACT FROM AUTHOR]

We previously reported that prostaglandin (PG)D2 and its isosteric analog, 11-deoxy-11-methylene-PGD2 (11d-11m-PGD2), promote adipogenesis in 3T3-L1 cells during the maturation phase. Focusing on the differentiation phase, although both PGs inhibited adipogenesis, this effect was canceled out by PGI2 and PGJ2 derivatives. Thus, PGD2 and 11d-11m-PGD2 play different roles during the phases, but do not affect PGI2 - and PGJ2-derivative-induced adipogenesis. [ABSTRACT FROM AUTHOR]

Purpose: Hemorrhagic cystitis (HC) which occurs in 9%--31% of recipients after hematopoietic stem cell transplantation (HSCT) is an important cause of morbidity and mortality. Various treatment approaches have been applied for such as conservative treatments (hydration, analgesic agents, antibiotics), intravesical treatments (bladder irrigation, hyaluronic acid, and prostaglandin E), intravenous or intravesical antiviral agents, hyperbaric oxygen, and surgical treatments. Materials and Methods: This retrospective study included two hundred thirty-three children who underwent HSCT in Pediatric Bone Marrow Transplantation unit between April 2010 and June 2017. Results: Ten patients (4.2%) developed HC. The mean age of patients was 12.8 years and the mean duration of the onset of HC was 20 days. Urine and blood BK polyomavirus were positive in nine and four patients, respectively. Six patients received intravesical hyaluronic acid, three patients received intravesical prostaglandin E, three patients received intravenous ganciclovir, two patients received intravenous and/or intravesical cidofovir and hyperbaric oxygen treatment. The mean time of recovery from hematuria was 43 days. This study showed that the BK polyomavirus has an important role in the development of HC in HSCT patients, as in harmony with the literature. HC has been successfully treated in eight patients with supportive measures and/or intravesical hyaluronic acid. Conclusions: BK polyomavirus plays an important role in the development of HC pediatric patients. Intravesical hyaluronic acid, besides supportive measures, was effective for the treatment of HC and hyperbaric oxygen may be reserved for refractory cases. [ABSTRACT FROM AUTHOR]