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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.

Hepatic inflammation is commonly identified in Wilson disease (WD), a genetic disease of hepatic and brain copper accumulation. Copper accumulation is associated with increased oxidative stress and reactive oxygen species generation which may result in non-enzymatic oxidation of membrane-bound polyunsaturated fatty acids (PUFA). PUFA can be oxidized enzymatically via lipoxygenases (LOX), cyclooxygenases (COX), and cytochrome P450 monooxygenases (CYP). Products of PUFA oxidation are collectively known as oxylipins (OXL) and are bioactive lipids that modulate hepatic inflammation. We examined hepatic OXL profiles at early stages of WD in two mouse models, the toxic milk mouse from The Jackson Laboratory (tx-j) and the Atp7b knockout on a C57Bl/6 background (Atp7b-/-B6). Targeted lipidomic analysis performed by ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry showed that in both tx-j and Atp7b-/-B6 mice, hepatic OXL profiles were altered with higher thromboxane and prostaglandins levels. The levels of oxidative stress marker, 9-HETE were increased more markedly in tx-j mice. However, both genotypes showed upregulated transcript levels of many genes related to oxidative stress and inflammation. Both genotypes showed higher prostaglandins, thromboxin along with higher PUFA-derived alcohols, diols, and ketones with altered epoxides; the expression of Alox5 was upregulated and many CYP-related genes were dysregulated. Pathway analyses show dysregulation in arachidonic acid and linoleic acid metabolism characterizes mice with WD. Our findings indicate alterations in hepatic PUFA metabolism in early-stage WD and suggest the upregulation of both, non-enzymatic ROS-dependent and enzymatic PUFA oxidation, which could have implications for hepatic manifestations in WD and represent potential targets for future therapies.

The aim of this study was to compare radiographic and clinical status and peri-implant sulcular fluid (PISF) prostaglandin E2 (PGE2) levels among patients with and without peri-implant disease. Patients with peri-implant mucositis (PiM) (Group 1) and peri-implantitis (Group 2) and individuals without peri-implant disease (Group 3) were included. Demographic information was collected, and peri-implant modified plaque and bleeding indices (mPI and mBI), probing depth (PD), and crestal bone loss (CBL) were recorded. PISF samples were collected and PGE2 levels measured. Statistical significance was set at P < .01. A total of 22 patients with PiM, 22 with peri-implantitis, and 23 without peri-implant disease (controls) were included. Scores of mPI (P < .01), mBI (P < .01), and PD (P < .01) were higher in patients with PiM and peri-implantitis than the controls. The volumes of collected PISF were significantly higher in patients with peri-implantitis (P < .01) compared to patients with PiM and the controls. The PISF volume was significantly higher in PiM patients (P < .01) than in the controls. There was a significant correlation between peri-implant PD and PISF PGE2 levels in patients with peri-implantitis (P < .001). Raised PISF PGE2 levels indicate poor peri-implant health; therefore, PGE2 is a potential biomarker for the assessment of peri-implant health status. [ABSTRACT FROM AUTHOR]

Recent research suggests that microbial molecules translocated from the intestinal lumen into the host's internal environment may play a role in various physiological functions, including sleep. Previously, we identified that butyrate, a short-chain fatty acid produced by intestinal bacteria, and lipoteichoic acid, a cell wall component of gram-positive bacteria, induce sleep when their naturally occurring translocation is mimicked by direct delivery into the portal vein. Building upon these findings, we aimed to explore the sleep signaling potential of intraportally administered lipopolysaccharide (LPS), a primary component of gram-negative bacterial cell walls, in rats. Low dose of LPS (1 μg/kg) increased sleep duration and prolonged fever, without affecting systemic LPS levels. Interestingly, administering LPS systemically outside the portal region at a dose 20 times higher did not affect sleep, indicating a localized sensitivity within the hepatoportal region for the sleep and febrile effects of LPS. Furthermore, both the sleep- and fever-inducing effects of LPS were inhibited by indomethacin, a prostaglandin synthesis inhibitor, and replicated by intraportal administration of prostaglandin E2 or arachidonic acid, suggesting the involvement of the prostaglandin system in mediating these actions. [ABSTRACT FROM AUTHOR]

• LPS-induced somnogenic and febrile effects are mediated by COX-2-dependent mechanism. • Sleep induced by tumor necrosis factor α is independent of COX-2-related signaling. • Spontaneous sleep is reduced in COX-2 KO mice at thermoneutral ambient temperatures. • COX-2-derived prostaglandins facilitate increased sleep in warm environment. • Homeostatic sleep responses to sleep loss are COX-2 independent. Prostaglandins (PGs) play a crucial role in sleep regulation, yet the broader physiological context that leads to the activation of the prostaglandin-mediated sleep-promoting system remains elusive. In this study, we explored sleep-inducing mechanisms potentially involving PGs, including microbial, immune and thermal stimuli as well as homeostatic sleep responses induced by short-term sleep deprivation using cyclooxygenase-2 knockout (COX-2 KO) mice and their wild-type littermates (WT). Systemic administration of 0.4 µg lipopolysaccharide (LPS) induced increased non-rapid-eye movement sleep (NREMS) and fever in WT animals, these effects were completely absent in COX-2 KO mice. This finding underscores the essential role of COX-2-dependent prostaglandins in mediating sleep and febrile responses to LPS. In contrast, the sleep and fever responses induced by tumor necrosis factor α, a proinflammatory cytokine which activates COX-2, were preserved in COX-2 KO animals, indicating that these effects are independent of COX-2-related signaling. Additionally, we examined the impact of ambient temperature on sleep. The sleep-promoting effects of moderate warm ambient temperature were suppressed in COX-2 KO animals, resulting in significantly reduced NREMS at ambient temperatures of 30 °C and 35 °C compared to WT mice. However, rapid-eye-movement sleep responses to moderately cold or warm temperatures did not differ between the two genotypes. Furthermore, 6 h of sleep deprivation induced rebound increases in sleep with no significant differences observed between COX-2 KO and WT mice. This suggests that while COX-2-derived prostaglandins are crucial for the somnogenic effects of increased ambient temperature, the homeostatic responses to sleep loss are COX-2-independent. Overall, the results highlight the critical role of COX-2-derived prostaglandins as mediators of the sleep-wake and thermoregulatory responses to various physiological challenges, including microbial, immune, and thermal stimuli. These findings emphasize the interconnected regulation of body temperature and sleep, with peripheral mechanisms emerging as key players in these integrative processes. [ABSTRACT FROM AUTHOR]

Background Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results and Conclusions Prostaglandins (PGs) have emerged as key drugs in second trimester medical abortion (STMA) and are currently a cornerstone in obstetric practice. Nevertheless, the application of PGs, integral to labor and abortion procedures, is not risk‐free, and has been associated with several complications, particularly maternal fever and uterine rupture (UR).The main outcome of the present systematic review was to assess the safety of PGs use in STMA, particularly in scarred uterus (SC).The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guideline. We performed a comprehensive systematic review by searching multiple databases, including MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database, and the research registers of Web of Science during the years 1990–2022.Only articles regarding cases of UR occurred after the use of PGs for STMA were included in the article. We excluded papers regarding UR during first trimester abortion induction of labor or pregnancy or unrelated to PGs use for STMA. Risk of bias was assessed employing a modified version of the “Newcastle‐Ottawa Scale” (NOS).A total of 178 studies were initially identified as potentially meeting the criteria for inclusion in the review. After full text evaluation, 110 other articles were excluded and 67 studies that suited the inclusion criteria were included. A total of 19 of the included studies were judged to have a high risk of bias. Given the heterogeneous nature of the findings, we opted for a narrative synthesis of the results.PGs appear to be an effective pharmacologic tool for STMA; however, their use is not entirely risk‐free. STMA requires well‐equipped obstetric centers with skilled clinicians and surgeons prepared for emergencies. Ultrasonographic scans should be routinely performed during STMA management, since a UR can also be silent during the induction of labor. Intrapartum transabdominal, transperineal, and transvaginal ultrasound may have the diagnostic potential to early recognize this obstetric emergency, to facilitate rapid medical and surgical treatment, improving the outcome. [ABSTRACT FROM AUTHOR]

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

Neural membranes are composed of phospholipids, sphingolipids, cholesterol, and proteins. In response to cell stimulation or injury, the metabolism of lipids generates various lipid mediators, which perform many cellular functions. Thus, phospholipids release arachidonic acid or docosahexaenoic acid from the sn-2 position of the glycerol moiety by the action of phospholipases A2. Arachidonic acid is a precursor for prostaglandins, leukotrienes, thromboxane, and lipoxins. Among these mediators, prostaglandins, leukotrienes, and thromboxane produce neuroinflammation. In contrast, lipoxins produce anti-inflammatory and pro-resolving effects. Prostaglandins, leukotrienes, and thromboxane are also involved in cell proliferation, differentiation, blood clotting, and blood vessel permeability. In contrast, DHA-derived lipid mediators are called specialized pro-resolving lipid metabolites (SPMs). They include resolvins, protectins, and maresins. These mediators regulate immune function by producing anti-inflammatory, pro-resolving, and cell protective effects. Sphingolipid-derived metabolites are ceramide, ceramide1-phosphate, sphingosine, and sphingosine 1 phosphate. They regulate many cellular processes, including enzyme activities, cell migration and adhesion, inflammation, and immunity. Cholesterol is metabolized into hydroxycholesterols and 7-ketocholesterol, which not only disrupts membrane fluidity, but also promotes inflammation, oxidative stress, and apoptosis. These processes lead to cellular damage. [ABSTRACT FROM AUTHOR]

Prostaglandins have many roles in the equine reproductive tract, including but not limited to luteolysis, luteal support, ovulation, transport through the uterine tube, uterine contraction, embryonic mobility, inflammation, and fibrosis. Altered secretion of inflammatory proteins are likely to disrupt the balance of endometrial function and could impair fertility. Our overall goal was to measure the expression of several prostaglandin- and inflammation-related genes in mares with different degrees of endometrial histological changes. Our hypothesis was that mares with neutrophilic and lymphocytic plasmocytic inflammation, fibrosis, or different biopsy grades would have altered concentrations of prostaglandin E2 (PGE2) and F2α (PGF2α), as well as altered expression of inflammation- and prostaglandin-related genes, compared to mares with minimal to no histological changes on biopsy evaluation. Forty-five endometrial biopsies from estrous mares were assessed by a reproductive pathologist for the degree of neutrophilic inflammation, lymphocytic and plasmocytic inflammation, and fibrosis, and a biopsy grade was assigned based on the Kenney-Doig system. A low-volume uterine lavage was collected from a subset of twenty-six mares prior to biopsy collection and was used to measure PGE2 and PGF2α concentrations via ELISA. Total RNA was extracted from biopsies and mRNA expression was evaluated for twenty-five genes of interest. A restricted maximum likelihood linear model was used to compare differences of mRNA expression, with a statistical significance set at P < 0.05. There was no difference in the abundance of PGE2 or PGF2α between any of the variables tested. Mares with endometrial biopsy grade I had lower expression of NF-kB, PTGS1 and HPGD compared to grade IIA or IIB (P < 0.05). Mares with neutrophilic inflammation had decreased expression of NF-kB, PTGS1, PTGER4, CBR1, mPGES2 and PTGIS compared to mares without inflammation. Mares with mild or minimal endometrial fibrosis had increased expression of mPGES2 and PTGIS , compared to mares with moderate endometrial fibrosis. In conclusion, several genes were identified to be differentially expressed in mares with histological changes compared to mares with no to minimal histological changes. The presence of inflammation and fibrosis may alter the concentration of prostaglandins in endometrial tissue, which could impair many of the uterine reproductive and immune functions during estrus, affecting early embryo survival. • Prostaglandins were differentially expressed based on histological assessment. • Prostaglandin expression was increased in IIA and IIB endometrial biopsies. • mPGES2 and PTGIS relative expression were decreased with moderate fibrosis. • Endometrial biopsies with inflammation had decreased prostaglandin expression. [ABSTRACT FROM AUTHOR]

An Aceclofenac jelly is a just emerging formulation which is used to relieve menstrual cramps. The main aim of study is to create and evaluate the oral medicated jellies of Aceclofenac. Aceclofenac has the ability to inhibit synthesis of prostaglandins by inhibiting the cyclo-oxygenase enzyme, these prostaglandins are responsible for pain. Heating and congealing method were used to produce the jelly using sugar, gelatin and china grass (agar agar). The formulated jellies were evaluated for physical appearance, dissolution, viscosity, pH, drug content, weight variation and stability studies. Formulation F6 was optimized based on the evaluation tests. The formulation F6 was further subjected to stability studies for 3 months according to ICH guidelines and it was found that nothing is altered that was able to be seen. [ABSTRACT FROM AUTHOR]

Our body temperature is normally kept within a narrow range of 1°C. For example, if our body temperature rises, such as in a hot environment or due to strenuous exercise, our thermoregulatory system will trigger a powerful heat defense response with vasodilation, sweating, and lowered metabolism. During fever, which often involves body temperatures of up to 41°C, this heat defense mechanism is apparently inhibited; otherwise, the rising body temperature would be immediately combated, and fever would not be allowed to develop. New evidence suggests how and where this inhibition takes place. In two consecutive studies from Cheng et al. and Xu et al., it has been shown that prostaglandin E2, which generates fever by acting on thermosensory neurons in the preoptic hypothalamus, also acts on neurons in the brainstem parabrachial nucleus, which receive temperature information from temperature-activated spinal cord neurons and relay this information to the thermoregulatory center in the hypothalamus to either induce cold or heat defenses. By acting on the same type of prostaglandin E2 receptor that is critical for fever generation in the preoptic hypothalamus, the EP3 receptor, prostaglandin E2 inhibits the signaling of the heat-responsive parabrachial neurons, while stimulating the cold-responsive neurons. These novel findings thus show that prostaglandin E2, by binding to the same receptor subtype in the parabrachial nucleus as in the preoptic hypothalamus, adjusts the sensitivity of the thermosensory system in a coordinated manner to allow the development of febrile body temperatures. [ABSTRACT FROM AUTHOR]

ABSTRACT Uterine vascular alterations take place in pyometra bitches speculatively influenced by prostaglandin and nitric oxide pathways. However, no causative effect of nitric oxide on endometrial vascularization was proved elsewhere for medically treated pyometra bitches. This study aimed to identify the main in situ uterine artery vasodilation pathway in pyometra bitches medically treated with antigestagen solely or coupled with prostaglandin. Pyometra bitches were enrolled into groups: Ovariohysterectomy at diagnosis (Control‐OHE; n = 7), Antigestagen (10 mg/kg aglepristone on Days 1, 2, and 8 after diagnosis; n = 5), and Antigestagen + luteolytic (aglepristone plus 1 μg/kg of cloprostenol from Days 1–7; n = 5). Treated bitches were ovariohysterectomized after 8 days of treatment. Uterine artery fragments from all bitches were collected for tissue nitric oxide and prostaglandin E2 assays. Control‐OHE group had lower uterine artery concentration of nitric oxide compared to treated bitches (Antigestagen and Antigestagen + luteolytic groups). No significant difference was verified between the medical treated groups. Uterine artery concentration of prostaglandin E2 was not different between control and treated bitches, as well as between both treated groups. In conclusion, nitric oxide and prostaglandin E2 are not directly involved in vascular modulation of the uterine artery, albeit pyometra medical treatment influences nitric oxide concentration in the uterine artery. [ABSTRACT FROM AUTHOR]

Prokineticin 1 (PROK1) is an important factor in pregnancy establishment in pigs, acting at the embryo–maternal interface and the corpus luteum (CL). Estradiol-17β (E2) is the primary pregnancy recognition signal in pigs, and its effects are augmented by luteotropic prostaglandin E2 (PGE2). On the contrary, prostaglandin F2α (PGF2α) exerts mainly a luteolytic effect. The present study aimed to elucidate whether E2, PGE2, and PGF2α regulate the expression of PROK1 and its receptors in the porcine CL and to determine the PROK1 effect on luteal endothelial cells and pathways that may be involved in this regulation. The effects of E2, PGE2, and PGF2α on the expressions of PROK1 and its receptors in the CL were studied using an in vitro model of ultrathin luteal tissue explants model. Additionally, the effects of E2 and PGE2 on the PROK1 system were determined using an in vivo approach, in which the hormones were administered into the uterine lumen to imitate their secretion by embryos. Endothelial cell proliferation was measured using the colorimetric method. E2 acting via estrogen receptors simulated the mRNA and protein expressions of PROK1 and PROKR1 in CL explants in vitro (p < 0.05). The simultaneous action of E2 with PGE2 enhanced the expression of luteal PROK1 mRNA in vitro (p < 0.05). Estradiol-17β acting alone significantly increased PROK1 mRNA levels in vivo, whereas E2 simultaneously administered with PGE2 significantly elevated the PROK1 mRNA expression and PROKR1 mRNA and protein contents in CLs adjacent to uterine horns receiving hormonal infusion compared with CLs adjacent to placebo-treated uterine horns (p < 0.01). The PROK1 protein expression was significantly higher in the CLs of pigs treated with E2, PGE2, and E2 together with PGE2 than in the control group. PGF2α increased the PROK1 mRNA content in CLs on days 12 and 14 of the estrous cycle (p < 0.05). The expression of PROKR2 at the mRNA and protein levels remained unchanged in response to in vitro and in vivo treatments. PROK1 stimulated the proliferation of luteal endothelial cells by activating the MAPK, AKT, and mTOR pathways (p < 0.05). In summary, the luteal expressions of PROK1 and PROKR1 in early pregnancy are regulated by E2 and PGE2. PROK1 stimulates luteal angiogenesis by activating the MAPK, AKT, and mTOR pathways. The regulation of luteal PROK1 expression by PGF2α indicates PROK1's putative role during luteolysis. We conclude that PROK1-PROKR1 signaling supports luteal function during CL rescue in pregnancy in pigs. [Display omitted] • Luteal expressions of prokineticin 1 and PROKR1 are regulated by primary embryonic signal (estradiol) and prostaglandin E2. • Luteolytic factor (prostaglandin F2α) is a putative regulator of luteal gene PROK1 expression during luteolysis. • Prokineticin 1 contributes to angiogenesis in the porcine CL by activation of MAPK, AKT and mTOR intracellular pathways. [ABSTRACT FROM AUTHOR]

From both pharmaceutical and structural perspectives, the large family of prostaglandins represent a truly remarkable class of natural products. Prostaglandin A2 is a tissue hormone naturally found in human seminal plasma and in the sea whip Plexaura homomalla with yet poorly understood biological or therapeutic effects. Herein, a novel strategy for the stereoselective construction of both naturally occurring prostaglandin A2 epimers and first insights into their functional effects on the major inhibitory neurotransmitter γ‐aminobutyric acid (GABA) type A receptors (GABAAR) are provided. The synthesis of both epimers was achieved in only 11 steps starting from commercially available 2,5‐dimethoxy‐tetrahydrofuran employing an organocatalytic domino‐aldol reaction, a Mizoroki‐Heck reaction, a Wittig reaction as well as an oxidation‐decarboxylation sequence. The (15R)‐epimer significantly reduced GABA‐induced currents through GABAA receptors while its (15S)‐epimer did not show any significant effect. These data suggest that (15R)‐PGA2 might serve as a novel scaffold for the development of selective GABAA receptor modulators. [ABSTRACT FROM AUTHOR]

This Perspectives article reflects on findings from our systematic review about adolescent dysmenorrhoea Q, drawing on sociology of diagnosis theory. We consider tensions and uncertainties between presentation with symptoms of dysmenorrhoea and processes of symptom categorisation and diagnosis in adolescents, tracing these through research and clinical guidance, considering possible implications for clinical practice. We argue that challenges in distinguishing between primary and secondary dysmenorrhoea in research translate into challenges in differentiation in clinical practice. We argue that framing this distinction as clear cut and straightforward belies the well-documented challenges in diagnosis of endometriosis, and that not recognising uncertainty and complexity inherent in this task may benefit neither clinicians nor patients. [ABSTRACT FROM AUTHOR]

From both pharmaceutical and structural perspectives, the large family of prostaglandins represent a truly remarkable class of natural products. Prostaglandin A2 is a tissue hormone naturally found in human seminal plasma and in the sea whip Plexaura homomalla with yet poorly understood biological or therapeutic effects. Herein, a novel strategy for the stereoselective construction of both naturally occurring prostaglandin A2 epimers and first insights into their functional effects on the major inhibitory neurotransmitter γ‐aminobutyric acid (GABA) type A receptors (GABAAR) are provided. The synthesis of both epimers was achieved in only 11 steps starting from commercially available 2,5‐dimethoxy‐tetrahydrofuran employing an organocatalytic domino‐aldol reaction, a Mizoroki‐Heck reaction, a Wittig reaction as well as an oxidation‐decarboxylation sequence. The (15R)‐epimer significantly reduced GABA‐induced currents through GABAA receptors while its (15S)‐epimer did not show any significant effect. These data suggest that (15R)‐PGA2 might serve as a novel scaffold for the development of selective GABAA receptor modulators. [ABSTRACT FROM AUTHOR]

Sonic Hedgehog (SHH) is a driver of embryonic patterning that, when corrupted, triggers developmental disorders and cancers. SHH effector responses are organized through primary cilia (PC) that grow and retract with the cell cycle and in response to extracellular cues. Disruption of PC homeostasis corrupts SHH regulation, placing significant pressure on the pathway to maintain ciliary fitness. Mechanisms by which ciliary robustness is ensured in SHH-stimulated cells are not yet known. Herein, we reveal a crosstalk circuit induced by SHH activation of Phospholipase A2α that drives ciliary E-type prostanoid receptor 4 (EP4) signaling to ensure PC function and stabilize ciliary length. We demonstrate that blockade of SHH-EP4 crosstalk destabilizes PC cyclic AMP (cAMP) equilibrium, slows ciliary transport, reduces ciliary length, and attenuates SHH pathway induction. Accordingly, Ep4-/- mice display shortened neuroepithelial PC and altered SHH-dependent neuronal cell fate specification. Thus, SHH initiates coordination between distinct ciliary receptors to maintain PC function and length homeostasis for robust downstream signaling. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is the most common fatal genetic disease among Caucasian people, with over 2000 mutations in the CFTR gene. Although highly effective modulators have been developed to rescue the mutant CFTR protein, unresolved inflammation and persistent infections still threaten the lives of patients. While the central role of arachidonic acid (AA) and its metabolites in the inflammatory response is widely recognized, less is known about their impact on immunomodulation and metabolic implications in CF. To this end, here we provided a comprehensive analysis of the AA metabolism in CF. In this context, CFTR dysfunction appeared to complexly disrupt normal lipid processing, worsening the chronic airway inflammation, and compromising the immune responses to bacterial infections. As such, potential strategies targeting AA and its inflammatory mediators are being investigated as a promising approach to balance the inflammatory response while mitigating disease progression. Thus, a deeper understanding of the AA pathway dysfunction in CF may open innovative avenues for designing more effective therapeutic interventions. [ABSTRACT FROM AUTHOR]

Drug-induced pigmentation (DIP) is estimated to account for 20% of all cases of acquired hyperpigmentation. Over 50 agents have been implicated, including antibiotics, antimalarials, antiretrovirals, antipsychotics, prostaglandin analogs, heavy metals, and chemotherapeutic agents. The skin, mucosal surfaces, nails, and hair can all be affected, with the color, distribution, onset, and duration of pigmentation varying between offending agents. Both a thorough physical examination and medication history are necessary to determine the offending agent. In terms of mechanism, DIP occurs most frequently through the accumulation of melanin within the dermis but also by drug accumulation, pigment synthesis, and iron deposition. Photoprotection, including applying a broad-spectrum sunscreen, wearing photoprotective clothing, and seeking shade, plays an important role in the prevention of exacerbation of DIP. Multiple lasers, including the picosecond alexandrite, Q-switched Nd:YAG, Q-switched alexandrite, and Q-switched ruby lasers, have been successful in obtaining clearance of DIP. In this review, we examine the unique characteristics of each of the inciting agents in terms of incidence, clinical presentation, time to onset and resolution, and pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Yoga may promote health via a complex modulation of inflammation. Little is known about oxylipins, a class of circulating mediators involved in inflammation resolution. Objective: To explore the acute effects of yoga exercise on systemic levels of oxylipins. Methods: This is a secondary analysis of a three-arm (high-intensity-yoga: HY, n = 10); moderate-intensity-yoga: MY, n = 10; and no-intervention-control: CON, n = 10) pilot randomized controlled trial employing a single bout of yoga exercise. Blood samples (baseline and 4-timepoint post-intervention) were used for an unbiased metabolipidomic profiling analysis. Net Areas Under the Curve per oxylipin were evaluated for each group. Results: Lipoxin(LX)B4, prostaglandin(PG)D2, and resolvin(Rv)D3 exhibited a greater magnitude of change in HY compared with MY and CON. Conclusion: Findings inform the design of future trials exploring the acute effects of yoga exercise on oxylipins' systemic levels. [ABSTRACT FROM AUTHOR]

Peptic ulcers, recognized for their erosive impact on the gastrointestinal mucosa, present a considerable challenge in gastroenterology. Epidemiological insights underscore the global prevalence of peptic ulcers, affecting 5–10+% of individuals, with a yearly incidence of 0.3 to 1.9 cases per thousand. Recent decades have witnessed a decline in complications, attributed to improved diagnostics and therapeutic advancements. The review deepens into H. pylori -associated and NSAID-induced ulcers, emphasizing their distinct prevalence in developing and industrialized nations, respectively. Despite advancements, managing peptic ulcers remains challenging, notably in H. pylori -infected individuals facing recurrence and the rise of antibiotic resistance. The pathophysiology unravels the delicate balance between protective and destructive factors, including the intricate molecular mechanisms involving inflammatory mediators such as TNF-α, ILs, and prostaglandins. Genetic and ethnic factors, rare contributors, and recent molecular insights further enhance our understanding of peptic ulcer development. Diagnostic approaches are pivotal, with upper gastrointestinal endoscopy standing as the gold standard. Current treatment strategies focus on H. pylori eradication, NSAID discontinuation, and proton pump inhibitors. Surgical options become imperative for refractory cases, emphasizing a comprehensive approach. Advances include tailored H. pylori regimens, the emergence of vonoprazan, and ongoing vaccine development. Challenges persist, primarily in antibiotic resistance, side effects of acid suppressants, and translating natural compounds into standardized therapies. Promising avenues include the potential H. pylori vaccine and the exploration of natural compounds, with monoterpenes showing therapeutic promise. This review serves as a compass, guiding healthcare professionals, researchers, and policymakers through the intricate landscape of peptic ulcer management. [ABSTRACT FROM AUTHOR]

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is associated with high levels of cysteinyl leukotrienes, prostaglandin D2, and low levels of prostaglandin E2. Further, 15-hydroxyeicosatetraenoic acid (15-HETE) levels may have predictive value in therapeutic outcomes of aspirin desensitization. Accumulation of nasal group 2 innate lymphoid cells (ILC2s) has been demonstrated during COX-1 inhibition in AERD, although the relationships between tissue ILC2 accumulation, reaction symptom severity, and novel lipid biomarkers are unknown. OBJECTIVE: We sought to determine whether novel lipid mediators are predictive of nasal ILC2 accumulation and symptom scores during COX-1 inhibitor challenge in patients with AERD. METHODS: Blood and nasal scraping samples from patients with AERD were collected at baseline and COX-1 inhibitor reaction and then processed for flow cytometry for nasal ILC2s and serum for lipidomic analysis. RESULTS: Eight patients with AERD who were undergoing aspirin desensitization were recruited. Of the 161 eicosanoids tested, 42 serum mediators were detected. Baseline levels of 15-HETE were negatively correlated with the change in numbers of airway ILC2s (r = -0.6667; P = .0428). Docosahexaenoic acid epoxygenase metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) was positively correlated with both changes in airway ILC2s (r = 0.7143; P = .0305) and clinical symptom scores (r = 0.5000; P = .0081). CONCLUSION: Low levels of baseline 15-HETE predicted a greater accumulation of airway ILC2s in patients with AERD who were receiving COX-1 inhibition. Further, increases in the cytochrome P pathway metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) were associated with increased symptoms and nasal ILC2 accumulation. Future studies to assess how these mediators might control ILC2s may improve the understanding of AERD pathogenesis.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) possess analgesic and anti-inflammatory properties by inhibiting cyclooxygenase (COX) enzymes. Conflicting evidence exists on whether NSAIDs influence signaling related to muscle adaptations and exercise with some research finding a reduction in muscle protein synthesis signaling via the AKT-mTOR pathway, changes in satellite cell signaling, reductions in muscle protein degradation, and reductions in cell proliferation. In this study, we determined if a single maximal dose of flurbiprofen (FLU), celecoxib (CEL), ibuprofen (IBU), or a placebo (PLA) affects the short-term muscle signaling responses to plyometric exercise. Methods: This was a block randomized, double-masked, crossover design, where 12 participants performed four plyometric exercise bouts consisting of 10 sets of 10 plyometric jumps at 40% 1RM. Two hours before exercise, participants consumed a single dose of celecoxib (CEL 200 mg), IBU (800 mg), FLU (100 mg) or PLA with food. Muscle biopsy samples were collected before and 3-h after exercise from the vastus lateralis. Data were analyzed using a repeated measures (RM) ANOVA, ANOVA, or a Friedman test. Significance was considered at p < 0.05. Results: We found no treatment effects on the mRNA expression of PTSG1, PTSG2, MYC, TBP, RPLOP, MYOD1, Pax7, MYOG, Atrogin-1, or MURF1 (all, p > 0.05). We also found no treatment effects on AKT-mTOR signaling or MAPK signaling measured through the phosphorylation status of mTORS2441, mTORS2448, RPS6 235/236, RPS 240/244, 4EBP1, ERK1/2, p38 T180/182 normalized to their respective total abundance (all, p > 0.05). However, we did find a significant difference between MNK1 T197/202 in PLA compared to FLU (p <.05). Conclusion: A single, maximal dose of IBU, CEL, or FLU taken prior to exercise did not affect the signaling of muscle protein synthesis, protein degradation, or ribosome biogenesis three hours after a plyometric training bout. [ABSTRACT FROM AUTHOR]

This experiment was performed to evaluate whether intrafollicular treatment of PGE2 or PGF2α administered in early estrus would induce normal ovulation, progesterone production (Experiment 1) and pregnancy (Experiment 2). In Experiment 1, mares in estrus after 2 days of endometrial edema were injected in all largest dominant follicles (28–35 mm in diameter) with 0.5 mL of sterile water containing 500 μg PGE2 (n = 6), 125 μg PGF2α (n = 6) or placebo (n = 7) (Hour 0). Ultrasound examinations were performed daily, until ovulation or anovulation was detected, and daily blood samples were taken for 8 days. In Experiment 2, mares with a dominant follicle ≥35 mm after at least three days of slight-to-moderate endometrial edema, were injected with 500 μg PGE2 diluted in 0.5 mL of sterile water for injection in the follicle (PGE2 group; n = 9 mares and 11 dominant follicles). No puncture was performed in the control group (n = 9 mares and 11 dominant follicles). Mares from both groups were inseminated. In Experiment 1, all mares (6/6) in the PGE2 group ovulated within 24 h of treatment. The mean interval from intrafollicular injection to ovulation was shorter (P < 0.001) in PGE2 mares (24 ± 0 h) than in control mares (77 ± 9 h). Mares from the PGF2α group developed hemorrhagic anovulatory follicles (HAF) more often (7/7) than control mares (2/7); P < 0.05). The progesterone concentration in mares from the PGF2α group was lower (P < 0.004) than control mares in the early post-ovulatory period. The first significant increase in post-ovulatory progesterone concentration occurred earlier (P < 0.05) in mares from the control group than in mares from the PGF2α and PGE2 groups. In Experiment 2, more mares from the control group (7/9, 78 %) became pregnant than from the PGE2 group (2/9, 22 %) (P = 0.015). In conclusion, PGE2 alone induced follicle collapse in all treated mares within 24 h of administrations, while PGF2α blocked ovulation and induced formation of HAFs. However, the post-ovulatory rise in progesterone production was delayed and the fertility reduced in mares with ovulation induced by PGE2 compared to control mares. • Intrafollicular administration of PGE2 at early-mid estrus hastened dramatically the time to ovulation. • The fertilization was possible, although the pregnancy rate was lower. • Intrafollicular administration of PGE2 at early-mid estrus did not alter progesterone secretion. • Intrafollicular administration of PGF2α alone blocked ovulation and induced formation of HAFs. [ABSTRACT FROM AUTHOR]

Dysmenorrhea is defined as “painful menstruation”. Two types of dysmenorrhea are known: primary, which occurs in the absence of any gynecological disease, and secondary, which is associated with an underlying pathology. Primary dysmenorrhea typically occurs approximately 6 months after menarche. Approximately 16% to 81% of women of childbearing age experience primary dysmenorrhea, with 2% to 29% reporting moderate to severe intensity. The treatment of primary dysmenorrhea focuses on pain relief. However, supplements such as Vitamin D3 and Zinc should be considered. Vitamin D3 inhibits prostaglandin synthesis, while zinc also inhibits its synthesis, thereby improving uterine microcirculation and reducing the intensity of uterine contractions. It is important to note that not only pharmacological treatment should be considered, but also lifestyle changes that promote maximum physical and emotional well-being to reduce the consumption of analgesics and achieve control or remission of the underlying pathology.

SARS-CoV-2 is an obligatory intracellular pathogen that requires a lipid bilayer membrane for its transport to build its nucleocapsid envelope and fuse with the host cell. The biological membranes are constituted by phospholipids (PLs), and vitamin E (Vit E) protects them from oxidative stress (OS). The aim of this study was to demonstrate if treatment with Vit E restores the modified profile of the FA in PLs in serum from patients with coronavirus disease-19 (COVID-19). We evaluated Vit E, total fatty acids (TFAs), fatty acids of the phospholipids (FAPLs), total phospholipids (TPLs), 8-isoprostane, thromboxane B2 (TXB2), prostaglandins (PGE2 and 6-keto-PGF1α), interleukin-6 (IL-6), and C-reactive protein (CRP) in serum from 22 COVID-19 patients before and after treatment with Vit E and compared the values with those from 23 healthy subjects (HSs). COVID-19 patients showed a decrease in Vit E, TPLs, FAPLs, and TFAs in serum in comparison to HSs (p ≤ 0.01), and Vit E treatment restored their levels (p ≤ 0.04). Likewise, there was an increase in IL-6 and CRP in COVID-19 patients in comparison with HSs (p ≤ 0.001), and treatment with Vit E decreased their levels (p ≤ 0.001). Treatment with Vit E as monotherapy can contribute to restoring the modified FA profile of the PLs in the SARS-CoV-2 infection, and this leads to a decrease in lipid peroxidation, OS, and the inflammatory process.

Francesco Oddone,1 Lucia Tanga,1 Sara Giammaria,1 Lorenzo Sabbatini,2 Alfonso Strianese,2 Manuela Ferrazza,1 Luca Mario Rossetti2 1IRCCS - Fondazione Bietti, Rome, Italy; 2Eye Clinic, ASST Santi Paolo E Carlo, University of Milan, Milan, ItalyCorrespondence: Francesco Oddone, Glaucoma Unit IRCCS Fondazione Bietti, Via Livenza 3, Roma, 00198, RM, Italy, Tel +39-06-85356727 ; +39-3291921575, Email odd1fr@gmail.comPurpose: The effectiveness, safety and tolerability of the preservative-free fixed combination of tafluprost and timolol (PF-TTFC) were evaluated over the 24-h in patients with open-angle glaucoma or ocular hypertension showing signs and symptoms of Ocular Surface Disease (OSD) and uncontrolled intraocular pressure (IOP) on prior benzalkonium chloride (BAK) – Latanoprost monotherapy.Methods: In this multi-center, prospective, interventional, non-comparative clinical trial, patients treated with BAK-Latanoprost underwent 24-h IOP measurements (8 am, 11 am, 2 pm, 5 pm, 8 pm, 11 pm, 2 am, 5 am) at baseline and after 3 months from switch to PF-TTFC. Mean 24-h IOP and daytime (8 am– 8 pm) vs nighttime (11 pm – 5 am) IOP were compared. Changes in OSD signs and symptoms, quality of life (QoL) and in-vivo corneal confocal microscopy (IVCM) were also evaluated.Results: Thirty-eight patients were analyzed. The mean 24-h IOP significantly decreased after 3 months from 17.8 mmHg (95% CI: 17.1– 18.6) to 15.3 mmHg (95% CI: 14.6– 16.1, p < 0.001). IOP was significantly reduced both at daytime (p < 0.001) and nighttime (p < 0.001), with better IOP control at night [− 2.9 (95% CI: − 3.5 to − 2.1) mmHg vs − 2.3 (95% CI: − 2.9 to − 1.6) mmHg]. In 20 patients (52.6%), corneal fluorescein staining improved, whereas in 4 patients (10.5%) it worsened. Hyperemia has improved in 24 (63.3%) patients and worsened in 2 (5.3%). Breakup time, Schirmer test and QoL scores showed no changes. At IVCM, the mean corneal wing-cell size was found significantly decreased (p < 0.005).Conclusion: The switch from BAK-Latanoprost to PF-TTFC significantly reduced IOP over the 24-h and improved OSD signs and symptoms.Keywords: glaucoma, tafluprost-timolol fixed combination, preservative free, BAK, prostaglandins, 24-h effectiveness, ocular surface disease

Objective: Oxylipins are bioactive lipids derived from polyunsaturated fatty acids (PUFAs) that modulate inflammation and may remain overexpressed in refractory synovitis. In plasma, they could also be biomarkers of synovial pathology. The aim of this study is to determine if synovial oxylipins in inflamed joints correlate with plasma oxylipins and with synovial histologic patterns. Methods: Patients with established rheumatoid or psoriatic arthritis with active disease despite treatment were recruited, and paired synovial tissue (ST) and plasma were collected. Oxylipins were determined by liquid chromatography with tandem mass spectrometry and were classified into groups according to their PUFA precursor and enzyme. The expression of CD20, CD68, CD3, and CD138 was obtained to describe synovial histology. Cell‐specific expression of oxylipin‐related genes was identified by examining available synovial single‐cell RNA sequencing data. Results: We included a total of 32 ST and 26 paired‐plasma samples. A total of 71 oxylipins were identified in ST, but only 24 were identified in plasma. Only levels of 9,10‐dihydroxyoctadecenoic acid and tetranor‐Prostaglandin FM had a significant positive correlation between plasma and ST. Several oxylipins and oxylipin‐related genes were differentially expressed among synovial phenotypes. Specifically, several 5‐lipoxygenase (LOX)–derived oxylipins were statistically elevated in the lympho‐myeloid phenotype and associated with B cell expression in rheumatoid arthritis samples. Conclusion: The lack of correlation between ST and plasma oxylipins suggests that ST lipid profiling better characterizes active pathways in treated joints. Synovial 5‐LOX–derived oxylipins were highly expressed in lympho‐myeloid–enriched synovium. Combination therapy with 5‐LOX inhibitors to improve refractory inflammation may be needed in patients with this histologic group. [ABSTRACT FROM AUTHOR]

Objective: Recently, two randomized controlled trials compared removal of cervical ripening balloon (CRB) after 6 versus 12 h. Their results showed similar Bishop score changes in both groups and a shorter time to delivery in the 6‐h group. Neither of the studies was powered to show difference in mode of delivery. The aim of this study was to compare mode of delivery when the CRB was removed after 6 versus 12 h. Methods: A historical control study comparing induction of labor with a CRB between two time periods, one in which the CRB was removed after 12 h (12‐h group), and the other in which it was removed after 6 h (6‐h group). We included term pregnancies with a singleton fetus in vertex presentation. We excluded patients with a previous cesarean delivery, failed ripening with prostaglandins prior to CRB insertion, and any contraindication for vaginal delivery. The primary outcome was mode of delivery. Secondary outcomes included delivery within 24 h and other maternal and neonatal outcomes. Results: We included 1704 patients, 914 in the 12‐h group, and 717 in the 6‐h group. Removal after 6 h was associated with a lower rate of cesarean and instrumental deliveries (28.6% vs 22.5%, and 12% vs 6.2%, respectively) and a higher rate of vaginal delivery within 24 h. All differences were statistically significant. Conclusion: Removing a cervical ripening balloon after 6 rather than 12 h is associated with reduced cesarean and instrumental delivery rates, and should be considered as a reasonable, and potentially superior alternative in labor induction protocols with intracervical ripening balloon. Synopsis: Removal of cervical ripening balloon after 6 versus 12 h was associated with lower cesarean delivery rates and higher vaginal delivery rates within 24 h. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the effect of administering a dose of gonadotropin (PG-600) in cows with persistent corpus luteum (PCL) which were treated with prostaglandin F2 a (PGF2a) and human chorionic gonadotropin (hCG). This study used 20, three-year-old cows diagnosed with PCL, had recently given birth, and were not pregnant. Cows were randomly allocated into groups T0, T1, T2 and T3. Cows in all groups were injected with PGF2a (25 mg/cow). Simultaneously, cows in groups T1, T2 and T3 were also injected with PG-600 at doses of 100, 150 and 200 IU/cow respectively. PGF2a and PG-600 were injected when PCL was identified. After that, cows showing signs of estrus were injected with hCG (100 IU/cow) and artificially inseminated 12-18 hours after the appearance of signs of estrus. AI was conducted using frozen thawed semen. Sixty days following AI, a pregnancy examination was conducted using USG. Estrus was detected in all treated cows, while the pregnancy rates varied. Compared with other groups, the groups given 100 and 150 IU PG-600 produced higher pregnancy rates. It could be concluded that the combination of 25 mg PGF2a, 150 IU PG-600, and 100 IU hCG was the most effective treatment to produce high pregnancy rates in cows with persistent corpus luteum. [ABSTRACT FROM AUTHOR]

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The aim was to compare reproductive outcomes of Nelore heifers submitted to timed AI (TAI) protocols, with 7 or 9 d of permanence of the intravaginal progesterone (P4) device and different times of prostaglandin F2α (PGF) administration, for first (n = 935) and second (n = 530) services. On Day −24, heifers without corpus luteum (CL) underwent a protocol for induction of ovulation. On Day 0, heifers received a P4 device (0.5 g) and 1.5 mg estradiol (E2) benzoate. In order for the TAI to be carried out on the same day, these treatments were performed 2 d later on the heifers treated with the 7-d protocol. Additionally, heifers received 0.5 mg PGF at different times, resulting in four experimental groups: 9dP4-PGFd9 (n = 365); 9dP4-PGFd7 (n = 369); 9dP4-PGFd0&9 (n = 364); 7dP4-PGFd0&7 (n = 367). These nomenclatures indicate for how many d the P4 device was kept and the specific day on which PGF was given. At P4 removal, all heifers received 0.5 mg E2 cypionate and 200 IU eCG, and TAI was performed 2 d later. Effects were considered significant when P ≤ 0.05 (superscript letters a,b) whereas a tendency was assumed when 0.05 < P ≤ 0.10. Groups 9dP4-PGFd0&9 and 7dP4-PGFd0&7 had lower percentage of heifers with CL at P4 removal. The diameter (mm) of the dominant follicle (DF) was affected by treatment at P4 removal (9dP4-PGFd9: 11.3 ± 0.3b; 9dP4-PGFd7: 11.8 ± 0.2ab; 9dP4-PGFd0&9: 12.6 ± 0.2a; 7dP4-PGFd0&7: 10.8 ± 0.2c) and at TAI (9dP4-PGFd9: 12.7 ± 0.3ab; 9dP4-PGFd7: 13.2 ± 0.2a; 9dP4-PGFd0&9: 13.4 ± 0.2a; 7dP4-PGFd0&7: 12.4 ± 0.3b). Expression of estrus (%) was affected by treatment (9dP4-PGFd9: 89.6a; 9dP4-PGFd7: 93.5a; 9dP4-PGFd0&9: 88.2ab; 7dP4-PGFd0&7: 85.6b). There were no differences among treatments for P/AI on Day 40 (30–35 d post AI), final P/AI (between Day 70 and parturition) and pregnancy loss (between Day 40 and final P/AI). When the permanence of the P4 device was compared, regardless of PGF treatments, 9-d protocols resulted in greater DF diameter at P4 removal and at TAI, and greater expression of estrus (90.4 vs. 85.6%) than the 7-d protocol. Despite that, the 7-d protocol resulted in greater P/AI on Day 40 (55.3 vs. 49.1%). In addition, there was an interaction between protocol duration and body weight, in which heavier heifers (≥ 307 kg) had greater P/AI when treated with the 7-d protocol, in comparison to 9-d. In conclusion, longer TAI protocols (9 d of P4 device duration) resulted in greater DF diameter and expression of estrus. However, the shorter TAI protocol (7 d of P4 device duration) produced greater P/AI on Day 40, particularly in heavier heifers. Within 9-d protocols, the additional dose of PGF on Day 0 or the anticipation of the PGF to Day 7 did not influence fertility. • 7 or 9 d of permanence of the P4 intravaginal device were evaluated in heifers. • PGF2α was administered at different times in E2/P4-based TAI protocols. • 9-d protocols resulted in larger DF and greater expression of estrus. • P/AI 30–35 d post AI was greater in heifers treated with 7-d protocol. • Heavier heifers had greater fertility when treated with the 7-d protocol. [ABSTRACT FROM AUTHOR]

Background: The implications of SARS‐CoV‐2 infection on male fertility remain largely unknown. Besides their well‐known pro‐ and anti‐inflammatory actions, prostaglandins and polyamines are present in semen, where they play key roles in sperm quality. Objectives: To analyze semen parameters, oxidative profile and the seminal fluid prostaglandin and polyamine systems in samples collected from individuals without coronavirus disease 2019 diagnosis and men who recovered from coronavirus disease 2019. Materials and methods: This study compared semen collected from men without positive coronavirus disease 2019 diagnosis with samples obtained from individuals 1–6 months and 7–30 months post SARS‐CoV‐2 infection. Semen parameters, thiobarbituric acid reactive substances, cyclooxygenase 2 expression by fluorescence immunocytochemistry and immunoblotting, prostaglandin levels by enzyme immunoassay, ornithine decarboxylase activity by a radioactive assay, and polyamine and acetylated polyamine levels by thin‐layer chromatography were assessed. Results: In both groups of semen samples from coronavirus disease 2019 recovered men, sperm vitality, total and progressive sperm motility, and putrescine levels were significantly decreased when compared with samples from the uninfected group. In contrast, lipid peroxidation, leukocyte‐associated cyclooxygenase 2 expression, and prostaglandin D2 levels were higher in semen from coronavirus disease 2019 recovered men than in samples from uninfected individuals. While sperm concentration and morphology, ornithine decarboxylase activity, and N‐acetylputrescine levels were statistically diminished in semen obtained up to 6 months after coronavirus disease 2019 recovery, these parameters remained unchanged when samples were collected 7–30 months after coronavirus disease 2019 recovery. Coronavirus disease 2019 vaccination did not show negative effects on any of the parameters evaluated. Discussion and conclusion: Our work provides insights into the detrimental impact of coronavirus disease 2019 on several sperm parameters, in some cases, even more than a year after SARS‐CoV‐2 infection, which would be accompanied by alterations in the seminal fluid prostaglandin and polyamine profiles. Therefore, future treatments targeting the prostaglandin and polyamine pathways in coronavirus disease 2019 recovered men could lead to a successful reinstatement of semen parameters. [ABSTRACT FROM AUTHOR]

Summary: The red alga Gracilaria vermiculophylla is a prostaglandin (PG)‐producing macroalga. The alga is rich in polyunsaturated fatty acids with 20 carbon atoms, mainly arachidonic acid (AA), which is a precursor of PGs. The purpose of the present study was to analyze the ability of the red alga to produce PGs using acetone powder as the crude enzyme prepared from the alga. The acetone powder (250 mg) was incubated with different amounts of exogenous AA (0.1–4 mg). For the determination of PG contents, 5 μL of a sample solution (5 mL in water) consisting of acetone powder and AA was injected into the HPLC column. For PG analysis, an HPLC system connected with a mass spectrometer was used. Results of the study showed that the released PGs from incubation of acetone powder and AA consisted of PGE2, 15‐keto‐PGE2, 15‐hydroperoxy‐PGE2, PGA2, and PGF2α. The capability of the crude enzyme prepared from the red alga to produce PGs was affected by available oxygen and AA concentrations. The crude enzyme (250 mg) was capable of producing 164 and 141 μg of PGE2 and 15‐keto‐PGE2, respectively, from incubation with 250 μg of AA. This in vitro method could be a simple way to provide PGs in the laboratory. [ABSTRACT FROM AUTHOR]

The travoprost intracameral implant was recently approved by the US Food and Drug Administration for sustained release medical treatment of open-angle glaucoma in the USA. The approval represents a substantial and progressive step forward in the area of sustained-release glaucoma therapy. Topical intraocular pressure-lowering medications for the treatment of glaucoma are faced with a host of challenges for long-term and usually lifelong care. A changing paradigm in glaucoma management involves first-line interventions with laser modalities, micro-invasive surgeries, and sustained-release treatment platforms. Future needs in the area of sustained-release therapy include a non-prostaglandin drug delivery platform and longer-term treatments that do not require surgical reintervention. [ABSTRACT FROM AUTHOR]

A method was developed for the determination of prostaglandin E2 in pork and lymph nodes based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Samples were extracted with acetonitrile, defatted with acetonitrile-saturated n-hexane, cleaned up by HLB solid-phase extraction columns, and the eluates were blown to near-dryness with nitrogen at 45 °C and determined by re-solubilizing in a 50% acetonitrile solution containing 0.2% formic acid. The separation was conducted on a C18 column with 0.1% formic acid solution and acetonitrile as mobile phases, and the multiple reaction monitoring was performed in negative ion mode. The limit of detection for prostaglandin E2 in pork and its products was 10 µg/kg, and the limit of quantification was 20 µg/kg. The recoveries of prostaglandin E2 in the method were in the range of 90~120%, and the precision was below 15.0%. The accuracy and precision of the method met the requirements for quantitative analysis. The values of prostaglandin E2 in non-lymph node samples were below the limit of quantification using the established method, and the range of prostaglandin E2 in lymph node samples was 20.7~101.0 µg/kg. By determining the amount of prostaglandin E2 in a sample, it can be used as an aid in identifying lymph nodes. This method is highly accurate and generalizable, and it provides strong technical support for combating the illegal use of lymph nodes. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common arrhythmia, and atrial fibrosis is a pathological hallmark of structural remodeling in AF. Prostaglandin I2 (PGI2) can prevent the process of fibrosis in various tissues via cell surface Prostaglandin I2 receptor (IP). However, the role of PGI2 in AF and atrial fibrosis remains unclear. The present study aimed to clarify the role of PGI2 in angiotensin II (Ang II)-induced AF and the underlying molecular mechanism. PGI2 content was decreased in both plasma and atrial tissue from patients with AF and mice treated with Ang II. Treatment with the PGI2 analog, iloprost, reduced Ang II-induced AF and atrial fibrosis. Iloprost prevented Ang II-induced atrial fibroblast collagen synthesis and differentiation. RNA-sequencing analysis revealed that iloprost significantly attenuated transcriptome changes in Ang II-treated atrial fibroblasts, especially mitogen-activated protein kinase (MAPK)-regulated genes. We demonstrated that iloprost elevated cAMP levels and then activated protein kinase A, resulting in a suppression of extracellular signal-regulated kinase1/2 and P38 activation, and ultimately inhibiting MAPK-dependent interleukin-6 transcription. In contrast, cardiac fibroblast-specific IP-knockdown mice had increased Ang II-induced AF inducibility and aggravated atrial fibrosis. Together, our study suggests that PGI2/IP system protects against atrial fibrosis and that PGI2 is a therapeutic target for treating AF. The prospectively registered trial was approved by the Chinese Clinical Trial Registry. The trial registration number is ChiCTR2200056733. Data of registration was 2022/02/12. [ABSTRACT FROM AUTHOR]

Endometritis is a common disease in animals, leading to disruption of reproductive processes and economic losses. Noradrenergic control of prostaglandin (PG)I2 formation by inflamed endometrium is unknown. We determined the involvement of α1-, α2- and β-adrenoreceptors (ARs) in noradrenaline-influenced PGI synthase (PGIS) protein abundance and PGI2 release from porcine (1) endometrial explants with Escherichia coli (E. coli)-induced inflammation in vivo, and (2) E. coli lipopolysaccharide (LPS)-treated endometrial epithelial cells. Experiment 1. E. coli suspension (E. coli group) or saline (CON group) was injected into the uterine horns. In both groups, noradrenaline increased endometrial PGIS abundance and PGI2 release versus the control values, and it was higher in the E. coli group than in the CON group. In the CON group, a noradrenaline stimulating effect on both parameters takes place through α1D-, α2C- and β2-ARs. In the E. coli group, noradrenaline increased PGIS abundance and PGI2 release via α1A-, α2(B,C)- and β(1,2)-ARs, and PGI2 release also by α2A-ARs. Experiment 2. LPS and noradrenaline augmented the examined parameters in endometrial epithelial cells versus the control value. In LPS-treated cells, β(1,2)-ARs mediate in noradrenaline excitatory action on PGIS protein abundance and PGI2 release. β3-ARs also contribute to PGI2 release. Under inflammatory conditions, noradrenaline via ARs increases PGI2 synthesis and release from the porcine endometrium, including epithelial cells. Our findings suggest that noradrenaline may indirectly affect processes regulated by PGI2 in the inflamed uterus. [ABSTRACT FROM AUTHOR]

In an effort to improve the spawning success rate in hypophysed pacu (Piaractus mesopotamicus) females, we investigated the effects of the time of administration and the concentration of Ciosin® (i.e., an analogue of prostaglandin F2α (PGF2α)) on ovulation. To that end, in Experiment 1, hypophysed females received 2 mL/fish of ciosin either at the time of the resolving dose (0H) or at five (5H) or seven hours (7H) postresolving dose. Then, in Experiment 2, hypophysed females were induced at the time of resolving the dose with five ciosin doses ranging from 1.0 to 7.0 mL/kg. Reproductive parameters and plasma levels of 17α-20β-dihydroxy-4-pregnen-3-one (DHP) and PGF2α were evaluated at the time of spawning for both experiments. Neither the timing of ciosin application closer to spawning nor its higher concentrations resulted in increased reproductive parameters or elevated PGF2α and DHP levels. The absence of the PGF2α peak at the time of ovulation in both experiments can be attributed to the rapid increase and subsequent decrease in exogenous PGF2α levels shortly after application. In Experiment 2 two main clusters were observed: one characterized by spawning failure, poor-quality spawn and low DHP levels and the other characterized by successful spawning, high fecundity and elevated DHP levels. Although positive correlations were observed between DHP and good reproductive performance, the reasons behind the substantial variation in DHP among females subjected to the same treatments remain unknown. An emerging focus is to elucidate the pattern of expression of PGF2α receptors and their relationship with DHP in pacu. [ABSTRACT FROM AUTHOR]

Introduction: Electroacupuncture (EA) has been applied in dysmenorrhea and has shown good efficacy. The mechanisms of EA are associated with autonomic nervous system adjustments and neuroendocrine regulation. Laser acupuncture (LA), however, has been widely investigated for its noninvasiveness. However, it remains uncertain whether LA is as effective as EA. This study aimed to compare EA and LA head to head in dysmenorrhea. Methods: A crossover, randomized clinical trial was conducted. EA or LA was applied to selected acupuncture points. Participants were randomized into two sequence treatment groups who received either EA or LA twice per week in luteal phase for 3 months followed by 2-month washout, then shifted to other groups (sequence 1: EA > LA; sequence 2: LA > EA). Outcome measures were heart rate variability (HRV), prostaglandins (PGs), pain, and quality-of-life (QoL) assessment (QoL-SF12). We also compared the effect of EA and LA in low and high LF/HF (low frequency/high frequency) status. Results: Totally, 43 participants completed all treatments. Both EA and LA significantly improved HRV activity and were effective in reducing pain (Visual Analog Scale [VAS]; EA: p < 0.001 and LA: p = 0.010) and improving QoL (SF12: EA: p < 0.001, LA, p = 0.017); although without intergroup difference. EA reduced PGs significantly (p < 0.001; δ p = 0.068). In low LF/HF, EA had stronger effects than LA in increasing parasympathetic tone in respect of percentage of successive RR intervals that differ by more than 50 ms (pNN50; p = 0.053) and very low-frequency band (VLF; p = 0.035). Conclusion: There is no significant difference between EA and LA in improving autonomic nervous system dysfunction, pain, and QoL in dysmenorrhea. EA is prominent in PGs changing and preserving vagus tone in low LF/HF; yet LA is noninvasive for those who have needle phobia. Whether LA is equivalent with EA and the mechanism warrants further study. Clinical trial identification number: NCT04178226. [ABSTRACT FROM AUTHOR]

This article, published in the Indian Journal of Medical & Paediatric Oncology, explores the role of prostaglandins secreted by senescent cells in inhibiting myoblast differentiation. The study found that senescent myoblasts secrete 15 deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ 2), which inhibits myoblast differentiation through the activation of the HRas-MAPK pathway. The researchers also discovered that 15d-PGJ 2 covalently modifies HRas at Cysteine 184, altering its intracellular distribution and activity, which is necessary for the inhibition of myoblast differentiation. This study suggests that the accumulation of senescent cells and the secretion of prostaglandins may contribute to chemotherapy-induced cachexia. [Extracted from the article]

Purpose: To analyze the medical management of primary open‑angle glaucoma (POAG) and ocular hypertension (OHT) and the placement of fixed‑drug combination drugs (FDC) in the treatment paradigm at a tertiary eye care center in South India. Methods: Retrospective study (January 2011–December 2015) of newly diagnosed POAG and OHT patients (≥18 years) with ≥5 years follow‑up. Primary outcome included percentage use of different antiglaucoma drugs (at initiation) and FDCs at the first, second, and third progression (sequencing). Secondary outcomes: Percentage discontinuation for different FDCs, efficacy parameters (decrease in intraocular pressure (IOP)/visual field), adverse events, and the median number of antiglaucoma medications (AGMs) after 5 years. Results: Three hundred and seventy eyes (198 patients) were analyzed; 84% of them had POAG. Prostaglandin analogs (PGAs) were the most common (66.2%). FDCs were started in 48 eyes (12.9%), with brimonidine + timolol combination being the most common. FDC usage at subsequent modifications was 10.1%, 24.04%, and 30.0%. Beta‑blockers and PGAs were the most frequently prescribed AGMs in our practice pattern, with β‑blockers being the most consistent one. Conclusion: This study is a fairly large study with a minimum of a 5‑year follow‑up of patients with POAG and OHT and gives insights into the treatment patterns, use of FDCs, and the need for multiple medications over time. [ABSTRACT FROM AUTHOR]

This study aimed to examine the changes in lower eyelid position after blepharoptosis surgery and the factors that influence the outcome. We conducted a retrospective study of 155 eyes of 89 patients who underwent blepharoptosis surgery between June 2019 and October 2022. The margin reflex distance (MRD)-1 and MRD-2 were examined preoperatively and 3 months postoperatively in two groups: one with lower scleral show (LSS) (n = 37) and one without LSS (n = 118). The clinical characteristics of the two groups were compared. Both the LSS and non-LSS groups showed significant postoperative improvement in MRD-1 scores (p <.01, p <.01, respectively). MRD-2 was significantly reduced in the LSS group, while it remained unchanged in the non-LSS group (p <.01, p =.27, respectively). There were no significant differences between the two groups in age, sex, history of hard contact lens use, preoperative levator function, use of topical steroids, history of endophthalmic surgery, or history of filtration surgery; however, the LSS group significantly used prostaglandin analogs (PGAs) (p =.03). Postoperatively, MRD-2 decreased in 13 eyes (35.1%) and was maintained in 24 eyes (64.9%) in the LSS group and was maintained in all eyes in the non-LSS group. In the LSS group, we also examined the association between postoperative MRD-2 reduction and the use of PGAs and found that more patients with MRD-2 reduction used PGAs (p =.02). Lower scleral show in PGAs-associated blepharoptosis is expected to improve after blepharoptosis surgery. [ABSTRACT FROM AUTHOR]

Objective Saline vaginal douching prior to intravaginal prostaglandin application might increase the vaginal pH, leading to improvement of prostaglandin bioavailability, by which the outcomes of labor induction can be greatly improved. Thus, we aimed to evaluate the effect of vaginal washing with normal saline before insertion of vaginal prostaglandin for labor induction. Study Design A systematic search was done in PubMed, Cochrane Library, Scopus, and ISI Web of Science from inception to March 2022. We selected randomized controlled trials (RCTs) that compared vaginal washing using normal saline versus no vaginal washing in the control group before intravaginal prostaglandin insertion during labor induction. We used RevMan software for our meta-analysis. Our main outcomes were the duration of intravaginal prostaglandin application, duration from intravaginal prostaglandin insertion to active phase of labor, duration from intravaginal prostaglandin insertion till total cervical dilatation, labor induction failure rate, incidence of cesarean section (CS), and rates of neonatal intensive care unit (NICU) admission and fetal infection postdelivery. Results Five RCTs were retrieved with a total number of 842 patients. Duration of prostaglandin application, duration from prostaglandin insertion to active phase of labor, and time interval from prostaglandin insertion to total cervical dilatation were significantly shorter among vaginal washing group (p < 0.05). Vaginal douching prior to prostaglandin insertion significantly decreased the incidence of failed labor induction (p < 0.001). After the removal of reported heterogeneity, vaginal washing was linked to a significant decline in CS incidence (p = 0.04). In addition, the rates of NICU admission and fetal infection were significantly lower in the vaginal washing group (p < 0.001). Conclusion Vaginal washing with normal saline before intravaginal prostaglandin insertion is a useful and easily applicable method for labor induction with good outcomes. Key Points Induction of labor is frequently used in the obstetrics field. We assessed vaginal washing impact before prostaglandin insertion for labor induction. Vaginal washing is an easily applicable method for labor induction with good outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Even though the local tolerance of prostaglandin (PG) analogues has improved drastically since the introduction of preservative-free (PF) eye drops, prescription patterns still vary widely among practitioners and between countries and could have an impact on the ocular surface of treated patients and, in consequence, their adherence. The aim of this study is to explore the prescribing patterns of PG analogues monotherapy in France and to evaluate their impact on ocular surface status. Methods: This was a national multicenter cross-sectional observational study that was conducted by 18 glaucoma experts in France. Patients over 18 years of age and receiving monotherapy with topical PG analogues for the treatment of ocular hypertension and/or glaucoma, with no history of prior glaucoma surgery, were consecutively selected from the glaucoma outpatient clinics of participating physicians and underwent an ocular surface examination. Results: A total of 344 eyes of 344 patients were enrolled between November 2022 and November 2023. Prescribed PG monotherapy was PF in 271 (78.7%) patients. Clinical history and ocular surface evaluation indicated that 79.4% of the study population (n = 273) presented with at least one symptom or clinical sign of dry eye and that three patients out of four had an unstable tear film. Subgroup analysis comparing preserved and PF PG analogues showed a higher prevalence of conjunctival hyperemia and corneal staining in the preserved group. Multivariate analysis identified conjunctival hyperemia as consistently associated with preservative use (odds ratio = 7.654; p = 0.003 for moderate conjunctival hyperemia). Conclusions: This study highlights the growing trend toward PF PG analogue prescriptions by specialists in France. However, ocular surface issues remain prevalent, impacting patient adherence and treatment efficacy. Comprehensive ocular surface examinations are crucial in glaucoma management to enhance long-term tolerance, compliance, and overall treatment success. [ABSTRACT FROM AUTHOR]

The efficiency of combining oestrous induction via a light program (16 h of light and 8 h of darkness for 60 days, ending on Day 0 – D0) with cloprostenol administration, followed by the male effect or not, was tested in acyclic Saanen goats during the non‐breeding season (June/2019 to January/2020). Initially, all animals (males and females) were submitted to the described light program; 60 days after its ending (D60), the females were divided into two groups, with (G1; n = 67) or without (G2; n = 61) a male effect from D60 to D75 after the light program. At D75, both groups received two cloprostenol doses (120 μg; intramuscular) 7.5 days apart (D75 and D82.5). Artificial insemination was performed at a specific time according to the oestrous onset (approximately 68.4 ± 1.2 h between the second cloprostenol dose and IA). Ultrasound scans were performed at different intervals to evaluate follicular dynamics and confirm pregnancy. At the first cloprostenol dose (D75), the proportion of does with at least a corpus luteum (CL), which indicates resumed cyclicity, was greater in G1 than in G2 (85.2% vs. 48.8%; p <.05), although no difference was found at the second dose (p >.05). The adjusted pregnancy rates (number of pregnant goats/oestrous goats) differed between G1 and G2 (21.7% vs. 42.0%; p <.05). G1 also showed a higher frequency of functional CL (based on blood flow and morphology) compared to G2 (96.9% vs. 66.7%; p <.05) at D116. A male effect using photo‐stimulated bucks after the first cloprostenol dose increased the number of does presenting CL after buck removal, and no impairment in the pregnancy rates of multiparous does was found. [ABSTRACT FROM AUTHOR]

Sub‐estrus buffaloes do not exhibit estrus signs despite being cyclic contributing to extended service periods and inter‐calving intervals causing significant economic loss. The present study described the effect of synthetic prostaglandin (PGF2α) on estrus behaviour, follicular and luteal morphometry, and serum estradiol (E2) and progesterone (P4) profile in sub‐estrus buffaloes during the non‐breeding season. The incidence of sub‐estrus was 38.4% during the non‐breeding season. The sub‐estrus buffaloes (n = 33) were divided into two groups, viz., Control (n = 16) and PGF2α treatment (Inj. Cloprostenol 500 μg, i.m., n = 17). Estrus induction response was significantly greater in the treatment (100 vs. 18.75%, p <.001), and a relatively greater proportion of animals conceived in the treatment group (29.41 vs. 6.25%, p =.08). The time elapsed to induction of estrus and insemination following treatment was significantly lower in the treatment group than control. A significant increment in the follicle diameter (9.72 ± 0.45 vs. 13.00 ± 0.45 mm, P <.0001) and serum estradiol (E2) concentration (66.01 ± 11.92 vs. 104.9 ± 13.21 pg/mL, p =.003) observed at the post‐treatment period in the PGF2α treatment group. At the same time, CL diameter was reduced significantly at a higher regression rate in the PGF2α treated buffaloes than those of control. Of the responded buffaloes, only 30% showed high‐intensity estrus attributed to the expulsion of cervico‐vaginal mucus (CVM), uterine tonicity, micturition, and mounting response by a teaser bull. From this study, it can be concluded that the administration of PGF2α could induce estrus in the sub‐estrus buffaloes during the non‐breeding season. Behavioural changes, along with sonographic observation of POF, regressing CL, and serum E2 and P4 concentration would be useful to determine the right time of insemination in sub‐estrus buffaloes during non‐breeding season. [ABSTRACT FROM AUTHOR]

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