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Lipid degradation is generally considered an antagonistic pathway to lipid synthesis, so this pathway is often removed to improve lipid production. In this study, triacylglycerol (TAG) cycling formed by lipid degradation is found to be crucial for long-chain polyunsaturated fatty acid (PUFA) biosynthesis; this result contradicts the notion that lipid degradation is a useless process. Specifically, we demonstrate that TAG cycling promoting PUFA biosynthesis occurred in Yarrowia lipolytica and Mortierella alpina via the desaturase/elongase pathway but not in Schizochytrium sp. with the polyketide synthase (PKS) pathway. Exploiting the TAG cycling mechanism, a strategy of decoupling the TAG biosynthesis and degradation is developed. Using this strategy, the titers of C20:5, C22:5 and prostaglandin F2α (PGF2α) in Y. lipolytica are improved by 116.2%, 99.4% and 41.7%, respectively. Our findings highlight the potential of the TAG cycling for related biochemical synthesis in the construction of excellent oleaginous engineered strains. The authors demonstrate the role and mechanism of triacylglycerol (TAG) cycling in polyunsaturated fatty acid biosynthesis and develop a strategy of decoupling the TAG biosynthesis and degradation to improve related biochemical synthesis.

Prostaglandins are thought to be important mediators in the initiation of human labour, however the evidence supporting this is not entirely clear. Determining how, and which, prostaglandins change during pregnancy and labour may provide insight into mechanisms governing labour initiation and the potential to predict timing of labour onset. The current study systematically searched the existing scientific literature to determine how biofluid levels of prostaglandins change throughout pregnancy before and during labour, and whether prostaglandins and/or their metabolites may be useful for prediction of labour. The databases EMBASE and MEDLINE were searched for English-language articles on prostaglandins measured in plasma, serum, amniotic fluid, or urine during pregnancy and/or spontaneous labour. Studies were assessed for quality and risk of bias and a qualitative summary of included studies was generated. Our review identified 83 studies published between 1968–2021 that met the inclusion criteria. As measured in amniotic fluid, levels of PGE 2 , along with PGF 2α and its metabolite 13,14-dihydro-15-keto-PGF 2α were reported higher in labour compared to non-labour. In blood, only 13,14-dihydro-15-keto-PGF 2α was reported higher in labour. Additionally, PGF 2α , PGF 1α , and PGE 2 were reported to increase in amniotic fluid as pregnancy progressed, though this pattern was not consistent in plasma. Overall, the evidence supporting changes in prostaglandin levels in these biofluids remains unclear. An important limitation is the lack of data on the complexity of the prostaglandin pathway outside of the PGE and PGF families. Future studies using new methodologies capable of co-assessing multiple prostaglandins and metabolites, in large, well-defined populations, will help provide more insight as to the identification of exactly which prostaglandins and/or metabolites consistently change with labour. Revisiting and revising our understanding of the prostaglandins may provide better targets for clinical monitoring of pregnancies. This study was supported by the Canadian Institutes of Health Research.

Heart failure (HF) is a cardiovascular disease affecting about 26 million people worldwide costing about $100 billons per year. HF activates several compensatory mechanisms and neurohormonal systems, so we hypothesized that the concomitant monitoring of a panel of potential biomarkers related to such conditions might help predicting HF evolution. Saliva analysis by point-of-care devices is expected to become an innovative and powerful monitoring approach since the chemical composition of saliva mirrors that of blood. The aims of this study were (i) to develop an innovative procedure combining MEPS with UHPLC-MS/MS for the simultaneous determination of 8-isoprostaglandin F and cortisol in saliva and (ii) to monitor lactate, uric acid, TNF-α, cortisol, α-amylase and 8-isoprostaglandin F concentrations in stimulated saliva samples collected from 44 HF patients during their hospitalisation due to acute HF. Limit of detection of 10 pg/mL, satisfactory recovery (95-110%), and good intra- and inter-day precisions (RSD ≤ 10%) were obtained for 8-isoprostaglandin F and cortisol. Salivary lactate and 8-isoprostaglandin F were strongly correlated with NT-proBNP. Most patients (about 70%) showed a significant decrease (a factor of 3 at least) of both lactate and 8-isoprostaglandin F levels at discharge, suggesting a relationship between salivary levels and improved clinical conditions during hospitalization.

Severe kinds of uterine inflammation in animals cause reproductive and economic problems. Although there are changes in prostaglandin (PG) production and noradrenergic uterine innervation during endometritis, the role of noradrenaline (NA) and adrenoreceptors (ARs) in PGF2α formation is not yet fully understood. To recognize noradrenergic control of the PGF2α generation on the cellular level during endometritis, the action of NA as well as α1-, α2- and β-ARs on protein abundances of PGF synthase (PGFS) and PG 9-ketoreductase/carbonyl reductase (CBR1) in the Escherichia coli lipopolysaccharide (LPS)-influenced pig endometrial epithelial cells and PGF2α release from these cells were studied. The epithelial cells were exposed to LPS and NA alone; LPS with NA; LPS with agonists of α1-, α2- and β-Ars; LPS with antagonists of β1-, β2- and β3-ARs with NA; and LPS with antagonists of β1-, β2- and β3-ARs in combinations with agonists of β1-, β2-, and β3-ARs for 24 h. PGFS and CBR1 protein abundances in cells were determined by Western blotting and PGF2α medium content by ELISA. LPS alone increased CBR1 protein abundance and PGF2α release by epithelial cells in reference to the control value. NA alone exerted a stimulatory effect on PGFS and CBR1 protein abundances and PGF2α secretion. After the exposure of cells to LPS with NA together, CBR1 protein abundance, as well as PGF2α release, was higher than in response to LPS and NA alone. PGFS protein abundance was increased by LPS with NA together compared to LPS action alone. In LPS-exposed endometrial epithelial cells, NA acting by β2- and β3-ARs leads to a rise in CBR1 protein abundance and PGF2α secretion. β2-ARs also participate in the NA excitatory effect on PGFS protein abundance. The NA effect on all the parameters tested is not mediated by α1- and α2-ARs. β2- and β3-ARs mediate the stimulatory effect of NA on PGF2α generation and secretion by the LPS-exposed pig endometrial epithelial cells. The results suggest that these cells may be a significant source of PGF2α under noradrenergic stimulation in the inflamed endometrium, and NA affects processes controlled by PGF2α during endometritis in an indirect manner.

In fish, prostaglandin F 2α is a female hormone regulating ovulation, but it is also a pheromone that triggers male reproductive behavior. In this study, the authors identified an olfactory receptor for prostaglandin F 2α , which, when mutated, leads to impaired courtship behavior in male zebrafish. Pheromones play vital roles for survival and reproduction in various organisms. In many fishes, prostaglandin F 2α acts not only as a female reproductive hormone, facilitating ovulation and spawning, but also as a sex pheromone inducing male reproductive behaviors. Here, we unravel the molecular and neural circuit mechanisms underlying the pheromonal action of prostaglandin F 2α in zebrafish. Prostaglandin F 2α specifically activates two olfactory receptors with different sensitivities and expression in distinct populations of ciliated olfactory sensory neurons. Pheromone information is then transmitted to two ventromedial glomeruli in the olfactory bulb and further to four regions in higher olfactory centers. Mutant male zebrafish deficient in the high-affinity receptor exhibit loss of attractive response to prostaglandin F 2α and impairment of courtship behaviors toward female fish. These findings demonstrate the functional significance and activation of selective neural circuitry for the sex pheromone prostaglandin F 2α and its cognate olfactory receptor in fish reproductive behavior.

PurposeBreath-hold diving results in significant changes in blood gases’ levels. Challenging variations in oxygen partial pressures may induce reactive oxygen species (ROS) production that exacerbate oxidative stress and, consequently, affect endothelial function. The aim of this study was to investigate the effects of breath-hold diving on oxidative stress damage, assessing ROS production. Nitric oxide metabolites, inducible nitric oxide synthase (iNOS), aminothiols, and renal function were evaluated too as markers of redox status and renal damage.MethodsROS production was assessed with electron paramagnetic resonance. Oxidative status values were measured at pre- and post-40 m dive in a deep swimming pool (Y-40) from six divers (mean age 46.6 ± 9.3 years; height 176 ± 4 cm; BMI 25 ± 2.9 kg/m2).ResultsSignificant (p < 0.05) increases at post-dive of ROS production rate (0.158 ± 0.003 vs 0.195 ± 0.006 μmol min−1), lipid peroxidation (8-isoprostane: 375.67 ± 195.62 vs 420.49 ± 232.31 pg mg−1 creatinine), nitrate (27.91 ± 19.71 vs 30.80 ± 20.44 μM), iNOS (31.30 ± 4.52 vs 35.68 ± 6.72 IU mL−1) and neopterin concentration (96.20 ± 40.41 vs 118.76 ± 27.84 μmol mol−1 creatinine) were recorded. Conversely, the antioxidant capacity significantly decreased (3.423 ± 0.089 vs 3.015 ± 0.284 mM) after immersion.ConclusionOverproduction of ROS and consequent oxidative damage to lipids of membrane and antioxidant capacity decreasing reflect also a hypoxic condition, which in the breath-hold diving typically occurs in the last few meters below the surface. iNOS produces NO in large quantities under the examined extreme conditions. Neopterin and creatinine concentration level increased, suggesting an “impairment of renal function” as a likely physiological response to PaO2 variations during dive activity.

Cyclic regression of the ovarian corpus luteum, the endocrine gland responsible for progesterone production, involves rapid matrix remodeling. Despite fibroblasts in other systems being known for producing and maintaining extracellular matrix, little is known about fibroblasts in the functional or regressing corpus luteum. Vast transcriptomic changes occur in the regressing corpus luteum, among which are reduced levels of vascular endothelial growth factor A (VEGFA) and increased expression of fibroblast growth factor 2 (FGF2) after 4 and 12 h of induced regression, when progesterone is declining and the microvasculature is destabilizing. We hypothesized that FGF2 activates luteal fibroblasts. Analysis of transcriptomic changes during induced luteal regression revealed elevations in markers of fibroblast activation and fibrosis, including fibroblast activation protein (FAP), serpin family E member 1 (SERPINE1), and secreted phosphoprotein 1 (SPP1). To test our hypothesis, we treated bovine luteal fibroblasts with FGF2 to measure downstream signaling, type 1 collagen production, and proliferation. We observed rapid and robust phosphorylation of various signaling pathways involved in proliferation, such as ERK, AKT, and STAT1. From our longer-term treatments, we determined that FGF2 has a concentration-dependent collagen-inducing effect, and that FGF2 acts as a mitogen for luteal fibroblasts. FGF2-induced proliferation was greatly blunted by inhibition of AKT or STAT1 signaling. Our results suggest that luteal fibroblasts are responsive to factors that are released by the regressing bovine corpus luteum, an insight into the contribution of fibroblasts to the microenvironment in the regressing corpus luteum. Summary Sentence Elevation of FGF2 expression during luteal regression may lead to alterations in the luteal microenvironment by stimulating proliferation of luteal fibroblasts and production of extracellular matrix. Graphical Abstract

Long-term use of topical prostaglandins might initiate chronic conjunctival inflammation, leading to poor outcomes of glaucoma surgery. The aim of this study was to evaluate the immunoexpression pattern of HSP70, CTGF, SNAIL, aSMA, cMYB, and HIFa in the conjunctiva, episclera, and deep sclera in patients with glaucoma undergoing deep sclerectomy in order to establish an association between staining intensities and prostaglandin F2 (PGF2) treatment. Double immunofluorescence (HSP70, CTGF, SNAIL, aSMA, cMYB, and HIFa) was performed on conjunctiva, episclera, and deep sclera samples, which were obtained from 23 patients treated with PGF2 and 8 patients without PGF2 treatment. When comparing the ocular tissues of patients regarding treatment with PGF2 analogs, we found a significant increase in the immunoexpression of HSP70 in the conjunctival epithelium of patients treated with PGF2 analogs compared to those without PGF2 treatment. These patients also had an increase in SNAIL immunoexpression and a decrease in aSMA immunoexpression in the deep sclera. There were no significant differences in HIFa, CTGF, or cMYB immunoexpression levels between the two groups. Further research into the regulation of these factors in ocular tissues could lead to the development of potential novel therapeutic approaches in glaucoma management.

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

Summary Low seminal plasma concentrations of coenzyme Q10 (CoQ10) have been correlated with impaired sperm parameters, but the exact mechanism remains of dominating interest. This randomised, placebo‐controlled study examined the effect of CoQ10 on catalase, superoxide dismutase (SOD) and F2‐isoprostanes in seminal plasma in infertile men and their relation with CoQ10 concentration. Sixty infertile men with idiopathic oligoasthenoteratozoospermia (OAT) were randomised to receive 200 mg d−1 of CoQ10 or placebo for 3 months. 47 persons of them completed the study. Semen analysis, anthropometric measurements, diet and physical activity assessment were performed for subjects before and after treatment. Independent and paired t‐test, chi‐square test and ancova were compared outcomes of supplementation between two groups. CoQ10 levels increased from 44.74 ± 36.47 to 68.17 ± 42.41 ng ml−1 following supplementation in CoQ10 (P < 0.001). CoQ10 group had higher catalase and SOD activity than the placebo group. There was a significant positive correlation between CoQ10 concentration and normal sperm morphology (P = 0.037), catalase (P = 0.041) and SOD (P < 0.001). Significant difference was shown between the mean of changes in seminal plasma 8‐isoprostane in two groups (P = 0.003) after supplementation. Three‐month supplementation with CoQ10 in OAT infertile men can attenuate oxidative stress in seminal plasma and improve semen parameters and antioxidant enzymes activity.