Prostaglandin Synthesis Research Articles

The effect of aspirin and eicosapentaenoic acid on urinary biomarkers of prostaglandin E2 synthesis and platelet activation in participants of the seAFOod polyp prevention trial.

Urinary prostaglandin (PG) E metabolite (PGE-M) and 11-dehydro (d)-thromboxane (TX) B2 are biomarkers of cyclooxygenase-dependent prostanoid synthesis. We investigated (1) the effect of aspirin 300 mg daily and eicosapentaenoic acid (EPA) 2000 mg daily, alone and in combination, on urinary biomarker levels and, (2) whether urinary biomarker levels predicted colorectal polyp risk, during participation in the seAFOod polyp prevention trial. Urinary PGE-M and 11-d-TXB2 were measured by liquid chromatography-tandem mass spectrometry. The relationship between urinary biomarker levels and colorectal polyp outcomes was investigated using negative binomial (polyp number) and logistic (% with one or more polyps) regression models. Despite wide temporal variability in PGE-M and 11-d-TXB2 levels within individuals, both aspirin and, to a lesser extent, EPA decreased levels of both biomarkers (74% [P ≤ .001] and 8% [P ≤ .05] reduction in median 11-d-TXB2 values, respectively). In the placebo group, a high (quartile [Q] 2-4) baseline 11-d-TXB2 level predicted increased polyp number (incidence rate ratio [IRR] [95% CI] 2.26 [1.11,4.58]) and risk (odds ratio [95% CI] 3.56 [1.09,11.63]). A low (Q1) on-treatment 11-d-TXB2 level predicted reduced colorectal polyp number compared to placebo (IRR 0.34 [0.12,0.93] for combination aspirin and EPA treatment) compared to high on-treatment 11-d-TXB2 values (0.61 [0.34,1.11]). Aspirin and EPA both inhibit PGE-M and 11-d-TXB2 synthesis in keeping with shared in vivo cyclooxygenase inhibition. Colorectal polyp risk and treatment response prediction by 11-d-TXB2 is consistent with a role for platelet activation during early colorectal carcinogenesis. The use of urinary 11-d-TXB2 measurement for a precision approach to colorectal cancer risk prediction and chemoprevention requires prospective evaluation.

Some Pathogenetic Aspects of Endocardial Endothelium Damage of Rats as a Result of Stress Effect Complicated by Hypercholesterolemia (original research)

The endothelial dysfunction is a predictor of occurrence for many diseases of cardiovascular system and a key link in their pathogenesis, formation and progression of clinical manifestations. Despite the large number of experimental and clinical researches, separate links of pathogenesis of heart endothelial cell damage under stress and in case of its combination with hypercholesterolemia require the further examination. The aim of the work was to investigate the role of nitric oxide, prostaglandins and antioxidants in the pathogenesis of endocardial endothelium damage (by the content of free fatty acids in it and the number of exfoliated cells) as a result of emotional and pain stress and stress complicated by hypercholesterolemia. An electro-impulse model was used to reproduce the stress. Alimentary hypercholesterolemia was modeled by keeping animals on an atherogenic diet for 2 months. To establish the role of individual pathogenetic links in the mechanisms of endotheliocyte damage, animals were administered the following pharmacological drugs: L-arginine (a substrate for the synthesis of nitric oxide), a prostaglandin synthesis blocker indomethacin, and prostenon (a synthetic analog of prostaglandin E2, which has an antioxidant effect). The state of endocardial endothelium was examined by using the light microscopy, analyzing the smears-imprints from macropreparations of ventricles by counting the number of endothelial cells in them. The content of free fatty acids was determined by the radiochemical method. It was shown that L-arginine significantly limits the damaging effect of the studied pathogenic factors on endocardial endothelium, reducing the number of exfoliated cells. The use of prostenon gives a slight, statistically unreliable positive effect. The use of indomethacin increases the damage of endothelial cells, which indicates the cytoprotective effect of prostaglandins under stress. All three studied preparations have no significant effect on the metabolism of free fatty acids both in case of “pure” emotional and pain stress and under stress complicated by hypercholesterolemia. The hypercholesterolemia of alimentary origin significantly limits the cytoprotective effect of L-arginine and prostenon on endocardial endothelium under stress action. In relation to indomethacin, in this situation, an increase of cell desquamation is observed, which indicates a decrease of prostaglandins protective effect.

Some aspects of the synthesis and modification of cross-conjugated cyclopentenone prostaglandins

Some aspects of the synthesis and modification of cross-conjugated cyclopentenone prostaglandins

Reactive Oxygen Species-Dependent Activation of EGFR/Akt/p38 Mitogen-Activated Protein Kinase and JNK1/2/FoxO1 and AP-1 Pathways in Human Pulmonary Alveolar Epithelial Cells Leads to Up-Regulation of COX-2/PGE2 Induced by Silica Nanoparticles.

The risk of lung exposure to silica nanoparticles (SiNPs) and related lung inflammatory injury is increasing with the wide application of SiNPs in a variety of industries. A growing body of research has revealed that cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) up-regulated by SiNP toxicity has a role during pulmonary inflammation. The detailed mechanisms underlying SiNP-induced COX-2 expression and PGE2 synthesis remain unknown. The present study aims to dissect the molecular components involved in COX-2/PGE2 up-regulated by SiNPs in human pulmonary alveolar epithelial cells (HPAEpiCs) which are one of the major targets while SiNPs are inhaled. In the present study, we demonstrated that SiNPs induced COX-2 expression and PGE2 release, which were inhibited by pretreatment with a reactive oxygen species (ROS) scavenger (edaravone) or the inhibitors of proline-rich tyrosine kinase 2 (Pyk2, PF-431396), epidermal growth factor receptor (EGFR, AG1478), phosphatidylinositol 3-kinase (PI3K, LY294002), protein kinase B (Akt, Akt inhibitor VIII), p38 mitogen-activated protein kinase (MAPK) (p38 MAPK inhibitor VIII), c-Jun N-terminal kinases (JNK)1/2 (SP600125), Forkhead Box O1 (FoxO1, AS1842856), and activator protein 1 (AP-1, Tanshinone IIA). In addition, we also found that SiNPs induced ROS-dependent Pyk2, EGFR, Akt, p38 MAPK, and JNK1/2 activation in these cells. These signaling pathways induced by SiNPs could further cause c-Jun and FoxO1 activation and translocation from the cytosol to the nucleus. AP-1 and FoxO1 activation could increase COX-2 and PGE2 levels induced by SiNPs. Finally, the COX-2/PGE2 axis might promote the inflammatory responses in HPAEpiCs. In conclusion, we suggested that SiNPs induced COX-2 expression accompanied by PGE2 synthesis mediated via ROS/Pyk2/EGFR/PI3K/Akt/p38 MAPK- and JNK1/2-dependent FoxO1 and AP-1 activation in HPAEpiCs.

Ambient PM2.5, inflammation, and prostaglandin synthesis: Evidence from a pregnancy cohort in Puerto Rico

Ambient PM2.5, inflammation, and prostaglandin synthesis: Evidence from a pregnancy cohort in Puerto Rico

PPARγ regulates lipid metabolism and viability of sheep trophoblast cells.

Peroxisome proliferator-activated receptor γ (PPARγ) is highly expressed in trophoblast tissues in pregnancy during which the protein participates in diverse events, including embryo implantation and placental formation. However, little is known about the role of PPARγ in embryonic development. This study investigated the function of PPARγ in sheep trophoblast cells. The coding sequence of sheep PPARγ encoded 475 amino acids and included one synonymou mutation compared with the sheep reference sequence for PPARγ. The PPARγ protein was localized in the nucleus and cytoplasm of sheep trophoblasts. The relative expression of PPARγ was elevated in cells treated with rosiglitazone and reduced following administration of GW9662. Activation of PPARγ promoted cell proliferation and mobility, but inhibited apoptosis. In addition, stimulation of PPARγ promoted the expression of lipid metabolism-related genes FABP4 and PLIN2. The expression of prostaglandin metabolism-related genes PLA2G4A, PTGS2 and PTGES also was upregulated significantly in trophoblast cells when PPARγ was activated. In contrast, activation of PPARγ did not impact expression of the prostaglandin-related genes PGFS and SLCO2A1. At the same time, activation of PPARγ activity increased the ratio of PGE2 to PGF2α. Furthermore, fluorescence labelling showed that the numbers of cell lipid droplets increased after stimulation of PPARγ activity, but decreased when PPARγ was inhibited. In conclusion, PPARγ is critical for the regulation of lipid metabolism and prostaglandin synthesis and secretion in sheep trophoblast cells and also has a potent effect on cell proliferation and viability.

Studies on <i>in vitro</i> binding of parecoxib to p38MAPK using spectroscopic methods

Purpose: To investigate the interaction between parecoxib and p38MAPK under simulated physiological conditions.Methods: The interaction between parecoxib and p38MAPK was studied under simulated physiological conditions using spectroscopy-based methods. The effect of parecoxib on the microenvironment and conformation of p38MAPK chromophore was studied by synchronous fluorescence spectroscopy, three-dimensional fluorescence, time-resolved fluorescence spectroscopy, circular dichroism spectroscopy, and ultraviolet-visible absorption spectroscopy.Results: Synchronous fluorescence spectroscopy showed that addition of parecoxib changed the structure of p38MAPK and destroyed the original stable structure. Three-dimensional fluorescence spectroscopy showed that the hydrophilicity of the microenvironment in which the fluorescent chromophore is located was enhanced, and the polarity increased such that the serum protein macromolecules tend to be unfolded, and the alpha-helix content reduced. Time-resolved fluorescence spectroscopy showed that the presence of parecoxib hardly affected the fluorescence quenching of p38MAPK, and the combination of parecoxib and p38MAPK forms a stable complex (static quenching). Circular dichroism spectroscopy revealed the combined parecoxib change, the secondary structure of p38MAPK and reduced the alpha-helix content. Ultraviolet-visible absorption spectroscopy revealed changes in the microenvironment of the three amino acid residues as well as the tertiary structure of the protein.Conclusion: The results shows that parecoxib has a significant effect on the structure of p38MAPK. In addition to explicitly inhibiting COX-2 and blocking arachidonic acid synthesis of prostaglandins, it inhibits the pathway involved in p38MAPK.

The role of CcPTGS2a in immune response against Aeromonas hydrophila infection in common carp (Cyprinus carpio)

Prostaglandin-endoperoxide synthase 2 (PTGS2), a crucial enzyme in prostaglandin synthesis, catalyzes the conversion of arachidonic acid to prostaglandins and plays a significant role in the inflammatory response. This investigation aimed to determine the regulatory role of PTGS2a in the innate immune response to bacterial infection in fish. To achieve this objective, the CcPTGS2a gene was identified and characterized in common carp (Cyprinus carpio), and its function in immune defense was investigated. According to the sequence and structural analysis results, CcPTGS2a had an open reading frame of 1806 bp that encoded 602 amino acids. It was estimated that the protein's theoretical molecular weight was 69.0 kDa, and its isoelectric point was 8.10. The structure of CcPTGS2a was observed to be conserved, with an epidermal growth factor domain and a peroxidase domain present. Moreover, the amino acid sequence of CcPTGS2a exhibited significant homology with the amino acid sequences of several fish species. CcPTGS2a mRNA was detected in the healthy tissues of common carp, with higher expression in the head kidney, spleen, gills, and liver. Following the challenges with Aeromonas hydrophila and lipopolysaccharide, CcPTGS2a mRNA showed unique geographic and temporal expression patterns, with significant increases detected in the head kidney, gills, spleen, and liver. Additionally, the recombinant CcPTGS2a protein exhibited detectable bacterial binding to various bacteria. As determined by subcellular localization analysis, CcPTGS2a was predominantly localized in the nucleus and cytoplasm. Furthermore, it was discovered that the overexpression of CcPTGS2a stimulated the up-regulation of ferroptosis-related genes and inflammatory cytokine mRNA expression in fish and EPC (Epithelioma papulosum cyprinid) cells while concurrently reducing the bacterial load of A. hydrophila. In contrast, the interference of CcPTGS2a decreased the mRNA expression of ferroptosis-related genes and inflammatory cytokines in fish and EPC cells and increased the bacterial load of A. hydrophila. Notably, A. hydrophila stimulation resulted in the up-regulation of CcPTGS2a protein expression in EPC cells. These results suggested that CcPTGS2a was involved in the immune response to bacterial infections in common carp.

15-lipoxygenase and cyclooxygenase expression profile and their related modulators in COVID-19 infection

BackgroundThe role of the lipoxygenase (LOX) and cyclooxygenase (COX) enzymes in maintaining cellular homeostasis and regulating immune responses promoted us in this study to analyze the pattern of changes in 15-lipoxygenase and cyclooxygenase isoforms and their related cytokines in SARS-CoV-2 infection. Methods15-LOX-1, 15-LOX-2, COX-1 and COX-2 gene expression levels were determined using qRT-PCR in nasopharynx specimens from patients with severe [N = 40] and non-severe [N = 40] confirmed SARS-CoV-2 infections and healthy controls. Circulating levels of lL-6, lL-10, PGE2, and IFN-γ were measured in patients and healthy controls using ELISA assay. The associations between the measured variables and the patient's clinic-pathological characteristics were assessed for all groups. ResultsThe expression level of 15-LOX-1 was elevated significantly in male patients with severe infection; although female patients showed a different expression profile. 15-LOX-2 expression level was considerably increased in male patients with severe infection; while changes in its expression remained inconclusive in female patients. The relationship between 15-LOX expression and the male gender was prominent. Both COX isoforms expression showed elevation in male and female patients that were correlated with disease severity. The simultaneous increase in lL-6, PGE2 and IFN-γ levels also decrease in lL-10 in patients with severe infection indicating the possible regulatory network related to the COX and 15-LOX enzymes in the output of the SARS-CoV-2 infection. ConclusionThe results of this study determined the pattern of possible changes in key enzymes of prostaglandin and eicosanoids synthesis pathway and their mediators, which can be helpful in mapping the SARS-CoV-2 pathogenicity and pharmaceutical approaches.

Stress-mediated aggregation of disease-associated proteins in amyloid bodies

The formation of protein aggregates is a hallmark of many neurodegenerative diseases and systemic amyloidoses. These disorders are associated with the fibrillation of a variety of proteins/peptides, which ultimately leads to cell toxicity and tissue damage. Understanding how amyloid aggregation occurs and developing compounds that impair this process is a major challenge in the health science community. Here, we demonstrate that pathogenic proteins associated with Alzheimer’s disease, diabetes, AL/AA amyloidosis, and amyotrophic lateral sclerosis can aggregate within stress-inducible physiological amyloid-based structures, termed amyloid bodies (A-bodies). Using a limited collection of small molecule inhibitors, we found that diclofenac could repress amyloid aggregation of the β-amyloid (1–42) in a cellular setting, despite having no effect in the classic Thioflavin T (ThT) in vitro fibrillation assay. Mapping the mechanism of the diclofenac-mediated repression indicated that dysregulation of cyclooxygenases and the prostaglandin synthesis pathway was potentially responsible for this effect. Together, this work suggests that the A-body machinery may be linked to a subset of pathological amyloidosis, and highlights the utility of this model system in the identification of new small molecules that could treat these debilitating diseases.

Primary hypertrophic osteoarthropathy: genetics, clinical features and management.

Primary hypertrophic osteoarthropathy (PHO) is a genetic disorder mainly characterized by clubbing fingers, pachydermia and periostosis. Mutations in the HPGD or SLCO2A1 gene lead to impaired prostaglandin E2 (PGE2) degradation, thus elevating PGE2 levels. The identification of the causative genes has provided a better understanding of the underlying mechanisms. PHO can be divided into three subtypes according to its pathogenic gene and inheritance patterns. The onset age, sex ratio and clinical features differ among subtypes. The synthesis and signaling pathways of PGE2 are outlined in this review. Cyclooxygenase-2 (COX-2) is the key enzyme that acts as the rate-limiting step for prostaglandin production, thus COX-2 inhibitors have been used to treat this disease. Although this treatment showed effective results, it has side effects that restrain its use. Here, we reviewed the genetics, clinical features, differential diagnosis and current treatment options of PHO according to our many years of clinical research on the disease. We also discussed probable treatment that may be an option in the future.

Effects of Dichlorodiphenyltrichloroethane on the Female Reproductive Tract Leading to Infertility and Cancer: Systematic Search and Review.

Persistent Organic Pollutants (POPs) such as dichlorodimethyltrichloroethane (DDT) are present and ubiquitous in the environment due to their resilient nature. DDT is a prevalent endocrine disruptor still found in detectable amounts in organisms and the environment even after its use was banned in the 1970s. Medline and Google Scholar were systematically searched to detect all relevant animal and human studies published in the last 20 years (January 2003 to February 2023) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. In total, 38 studies were included for qualitative synthesis. This systematic search and review indicated that exposure to DDT is associated with female reproductive health issues, such as reduced fecundability; increased risk of preterm/premature deliveries; increased periods of gestation; alterations in the synthesis of crucial reproductive hormones (Progesterone and Oxytocin) through ion imbalances and changes in prostaglandin synthesis, myometrial and stromal hypertrophy, and edema; and variations in uterine contractions through increased uterine wet weight. There was also limited evidence indicating DDT as a carcinogen sufficient to instigate reproductive cancers. However, this review only takes into account the in vitro studies that have established a possible pathway to understand how DDT impacts female infertility and leads to reproductive cancers. Links between the pathways described in various studies have been developed in this review to produce a summarized picture of how one event might lead to another. Additionally, epidemiological studies that specifically targeted the exposure to DDT of females belonging to various ethnicities have been reviewed to develop an overall picture of prevailing female reproductive health concerns in different nations.

Evolving immunometabolic response to the early Leishmania infantum infection in the spleen of BALB/c mice described by gene expression profiling

Transcriptional analysis is a useful approximation towards the identification of global changes in host-pathogen interaction, in order to elucidate tissue-specific immune responses that drive the immunopathology of the disease. For this purpose, expression of 223 genes involved in innate and adaptive immune response, lipid metabolism, prostaglandin synthesis, C-type lectin receptors and MAPK signaling pathway, among other processes, were analyzed during the early infection in spleens of BALB/c mice infected by Leishmania infantum. Our results highlight the activation of immune responses in spleen tissue as early as 1 day p.i., but a mixed pro-inflammatory and regulatory response at day 10 p.i., failing to induce an effective response towards control of Leishmania infection in the spleen. This ineffective response is coupled to downregulation of metabolic markers relevant for pathways related to icosanoid biosynthesis, adipocytokine signaling or HIF-1 signaling, among others. Interestingly, the over-representation of processes related to immune response, revealed Il21 as a potential early biomarker of L. infantum infection in the spleen. These results provide insights into the relationships between immune and metabolic responses at transcriptional level during the first days of infection in the L. infantum-BALB/c experimental model, revealing the deregulation of many important pathways and processes crucial for parasitic control in infected tissues.

Panax quinquefolius saponins combined with dual antiplatelet therapy enhanced platelet inhibition with alleviated gastric injury via regulating eicosanoids metabolism

BackgroundPanax quinquefolius saponin (PQS) was shown beneficial against platelet adhesion and for gastroprotection. This study aimed to investigate the integrated efficacy of PQS with dual antiplatelet therapy (DAPT) on platelet aggregation, myocardial infarction (MI) expansion and gastric injury in a rat model of acute MI (AMI) and to explore the mechanism regarding arachidonic acid (AA)-derived eicosanoids metabolism.MethodsWistar rats were subjected to left coronary artery occlusion to induce AMI model followed by treatment with DAPT, PQS or the combined therapy. Platelet aggregation was measured by light transmission aggregometry. Infarct size, myocardial histopathology was evaluated by TTC and H&E staining, respectively. Gastric mucosal injury was examined by scanning electron microscope (SEM). A comprehensive eicosanoids profile in plasma and gastric mucosa was characterized by liquid chromatography-mass spectrometer-based lipidomic analysis.ResultsPQS+DAPT further decreased platelet aggregation, lessened infarction and attenuated cardiac injury compared with DAPT. Plasma lipidomic analysis revealed significantly increased synthesis of epoxyeicosatrienoic acid (EET) and prostaglandin (PG) I2 (potent inhibitors for platelet adhesion and aggregation) while markedly decreased thromboxane (TX) A2 (an agonist for platelet activation and thrombosis) by PQS+DAPT, relative to DAPT. DAPT induced overt gastric mucosal damage, which was attenuated by PQS co-administration. Mucosal gastroprotective PGs (PGE2, PGD2 and PGI2) were consistently increased after supplementation of PQS+DAPT.ConclusionsCollectively, PQS+DAPT showed synergistic effect in platelet inhibition with ameliorated MI expansion partially through upregulation of AA/EET and AA/PGI2 synthesis while suppression of AA/TXA2 metabolism. PQS attenuated DAPT-induced gastric injury, which was mechanistically linked to increased mucosal PG production.

The vasoactive effects of bradykinin, vasoactive intestinal peptide, calcitonin gene-related peptide and neuropeptide Y depend on the perivascular tissue in porcine retinal arterioles in vitro.

The retina contains a number of vasoactive neuropeptides and corresponding receptors, but the role of these neuropeptides for tone regulation of retinal arterioles has not been studied in detail. Porcine arterioles with preserved perivascular retinal tissue were mounted in a wire myograph, and the tone was measured after the addition of increasing concentrations of bradykinin, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP) and brain natriuretic peptide (BNP). The experiments were performed during inhibition of the synthesis of nitric oxide (NO), prostaglandins and dopamine and were repeated after removal of the perivascular retinal tissue. Bradykinin, VIP and CGRP induced significant concentration-dependent dilatation and NPY significant concentration-dependent contraction of the arterioles in the presence of perivascular retinal tissue (p < 0.03 for all comparisons) but not on isolated arterioles. BNP and SP had no effect on vascular tone. The NOS inhibitor L-NAME reduced bradykinin- and VIP-induced relaxation (p < 0.001 for both comparisons), whereas none of the other inhibitors influenced the vasoactive effects of the studied neuropeptides. The effects of neuropeptides on the tone of retinal arterioles depend on the perivascular retinal tissue and may involve effects other than those mediated by nitric oxide, prostaglandins and adrenergic compounds. Investigation of the mechanisms underlying the vasoactive effect of neuropeptides may be important for understanding and treating retinal diseases where disturbances in retinal flow regulation are involved in the disease pathogenesis.

MFSD2A potentiates gastric cancer response to anti-PD-1 immunotherapy by reprogramming the tumor microenvironment to activate T cell response.

The efficacy of anti-programmed cell death protein 1 (PD-1) immunotherapy in various cancers, including gastric cancer (GC), needs to be potentiated by more effective targeting to enhance therapeutic efficacy or identifying accurate biomarkers to predict clinical responses. Here, we attempted to identify molecules predicting or/and promoting anti-PD-1 therapeutic response in advanced GC (AGC). The transcriptome of AGC tissues from patients with different clinical responses to anti-PD-1 immunotherapy and GC cells was analyzed by RNA sequencing. The protein and mRNA levels of the major facilitator superfamily domain containing 2A (MFSD2A) in GC cells were assessed via quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry. Additionally, the regulation of anti-PD-1 response by MFSD2A was studied in tumor-bearing mice. Cytometry by Time-of-Flight, multiple immunohistochemistry, and flow cytometry assays were used to explore immunological responses. The effects of MFSD2A on lipid metabolism in mice cancer tissue and GC cells was detected by metabolomics. Higher expression of MFSD2A in tumor tissues of AGC patients was associated with better response to anti-PD-1 immunotherapy. Moreover, MFSD2A expression was lower in GC tissues compared to adjacent normal tissues, and its expression was inversely correlated with GC stage. The overexpression of MFSD2A in GC cells enhanced the efficacy of anti-PD-1 immunotherapy in vivo by reprogramming the tumor microenvironment (TME), characterized by increased CD8+ T cell activation and reduced its exhaustion. MFSD2A inhibited transforming growth factor β1 (TGFβ1) release from GC cells by suppressing cyclooxygenase 2 (COX2)-prostaglandin synthesis, which consequently reprogrammed TME to promote anti-tumor T cell activation. MFSD2A potentially serves as a predictive biomarker for anti-PD-1 immunotherapy response in AGC patients. MFSD2A may be a promising therapeutic target to potentiate the efficacy of anti-PD-1 immunotherapy by reprogramming the TME to promote T cells activation.

A complete prostaglandin pathway from synthesis to inactivation in the oral gland of the jawless vertebrate lamprey, Lethenteron camtschaticum

Information on the prostaglandin pathway in lampreys is limited. Here, five genes related to the prostaglandin pathway from synthesis to inactivation, namely, phospholipase A2, cyclooxygenase-2, prostaglandin E synthase 3, prostaglandin D synthase, and 15-hydroxyprostaglandin dehydrogenase [NAD(+)], were screened and cloned from the lamprey, Lethenteron camtschaticum. Bioinformatic analysis showed that these lamprey genes are relatively conserved with teleost genes in domains, motifs, gene structure and 3D structure. Analysis of expression distribution of the genes in lamprey tissues revealed that a complete prostaglandin pathway from synthesis to inactivation exists in the oral gland of lamprey, especially the key gene of prostaglandin synthesis cyclooxygenase-2, which was highly expressed in the oral gland. Furthermore, cyclooxygenase-2 expression increased after LPS and Poly I:C stimulations. Using our established spatial metabolite database LampreyDB, six prostaglandin-related metabolites were screened from the oral gland of lamprey, four of which were highly expressed in the oral gland. This study provides new insights into prostaglandin synthesis and inactivation pathways in lamprey, thereby improving our understanding of the origin and evolution of the prostaglandin pathway and contributing to the recognition of lamprey regulatory mechanisms in development and immunity.

Xanthatin suppresses pancreatic cancer cell growth via the ROS/RBL1 signaling pathway: In vitro and in vivo insights

BackgroundAs a malignant digestive system tumor, pancreatic cancer has a high mortality rate. Xanthatin is a sesquiterpene lactone monomer compound purified from the traditional Chinese herb Xanthium strumarium L. It has been reported that Xanthatin exhibits inhibitory effects on various cancer cells in retinoblastoma, glioma, hepatoma, colon cancer, lung cancer, as well as breast cancer. However, in pancreatic cancer cells, only one report exists on the suppression of Prostaglandin E2 synthesis and the induction of caspase 3/7 activation in Xanthatin-treated MIA PaCa-2 cells, while systematic in vitro and in vivo investigations and related mechanisms have yet to be explored. PurposeThis research aims to explore the in vitro and in vivo effects of Xanthatin on pancreatic cancer and its molecular mechanisms. MethodsThe anticancer effects and mechanisms of Xanthatin on pancreatic cancer cells were assessed through employing cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay, carboxyfluorescein diacetate succinimidyl ester (CFDA SE) cell proliferation assay, colony formation assay, wound healing assay, transwell assay, Annexin V-FITC/propidium iodide (PI) dual staining, Hoechst nuclear staining, Western blot analysis, phosphoproteomics, and reactive oxygen species (ROS) measurement. The in vivo anticancer effects of Xanthatin on pancreatic cancer cells were studied using a nude mouse model. ResultsThe present study showed that Xanthatin can prevent the proliferation and metastasis of pancreatic cancer cells and trigger the exposure of phosphatidylserine (PS), chromatin condensation, and caspase activation, thereby inducing apoptosis. Phosphoproteomic analysis indicated that Xanthatin inhibits the phosphorylation of the proliferation-associated protein RBL1, and oxidative stress can lead to RBL1 dephosphorylation. Further investigation revealed that Xanthatin significantly upregulates ROS levels in pancreatic cancer cells, and the antioxidant N-acetylcysteine (NAC) can reverse Xanthatin-induced cell proliferation inhibition and apoptosis. In addition, Xanthatin can suppress pancreatic cancer cell growth in a xenograft nude mouse model with low toxicity to the mice. ConclusionXanthatin may inhibit the proliferation of pancreatic cancer cells and trigger apoptosis through the ROS/RBL1 signaling pathway.

Clinical Effects of Cervical Dilation Balloon and Castor Oil Meal Nursing Interventions in Term Induction of Labor

This study analyzed the clinical effects of cervical dilation balloon and castor oil meal nursing interventions in term induction of labor. The eighty pregnant women who were scheduled for delivery in our hospital between March 2020 and January 2022 were recruited into an observation group and a control group using a random number table. The control group received oxytocin for labor induction while the observation group received cervical dilation balloon and castor oil meal nursing interventions for labor induction. In addition to clinical treatment experiments, cell experiments are performed. BeWo cells were cultured to study the effect of estrogen on cell viability, and the expression of matrix metalloproteinase 2 and 9 (MMP2, MMP9) was detected using Western blotting. The endpoints of this study were to investigate the impact of estrogen changes on term-induced pregnant women and to compare the cervical dilation balloon and castor oil meal nursing interventions with regards to duration of labor, efficacy of cervical ripening, Bishop score of the cervix, postpartum complications, and other relevant indicators. The viability of BeWo cells did not significantly differ after treatment with different concentrations of 17β-E2 (-&gt; 0.05). The expression of MMP9 after different levels of treatment did not significantly differ (P &gt;0.05), whereas the expression of MMP2 protein in the 5×10−7 and 5×10−8 M treatment groups was lower than that in the control group (P &lt;0.05). The first stage and total duration of labor were significantly shorter in the observation group than that in the control group (P &lt;0.05). The efficacy of cervical ripening was significantly higher in the observation group than that in the control group (P &lt;0.05). The Bishop score of the cervix was significantly higher in the observation group after intervention (P &lt;0.05). The incidence of complications in the observation group was significantly lower than that in the control group (P &lt;0.05). Estrogen levels may affect the invasive function of trophoblast cells, causing abnormal placental function. Castor oil has hormonal effects and contains precursors for prostaglandin synthesis and can induce and strengthen contractions, soften the cervix, and dilate the cervix. The combined use of cervical dilation balloon and castor oil meal in term induction of labor has clear clinical effects, including the effective shortening of labor duration, favorable cervical ripening, significant improvement in the Bishop score of the cervix, and reduced incidence of complications. This study suggests its potential for clinical application and wider use.

Comparison of Effectivenness Between Ibuprofen and Paracetamol in the Treatment of Fever in Children Aged 0-18 Years a Systematic Review and Meta-Analysis of Randomized Control Trials

Fever is defined as one of the acute adaptive physiological responses to conditions caused by infection, characterized by an increase in body temperature ?38°C. Acetaminophen (paracetamol) and ibuprofen are the only two choices of over-the-counter drugs for the antipyretic class. Acetaminophen (paracetamol) and ibuprofen are the two over-the-counter drug choices, the only antipyretic class most often prescribed to treat fever in children. Acetaminophen (paracetamol) is considered the safest over-the-counter drug to control fever in children, while ibuprofen is a non-steroidal anti-inflammatory drug that works by inhibiting the synthesis of prostaglandin E2 in the anterior hypothalamus thereby reducing the temperature regulation center and can achieve a cooling effect. This made the authors interested in presenting a systematic review to compare the antipyretic profiles of acetaminophen with ibuprofen in the treatment of fever in children aged 0-18 years. Articles were searched through the database from January 2019 - January 2022. Searches were obtained from the PUBMED database. There was no attempt by the authors to specifically search for unpublished articles in English or Indonesian. Free full text or articles that can be downloaded for free (open access) articles with randomized controlled trials. The subjects used were children aged 0-18 years. Based on research results that ibuprofen is more effective than acetaminophen in treating fever in children. This was evidenced from the 8 articles discussed, 4 of which said that the use of ibuprofen was more effective in lowering body temperature, while 3 articles concluded that both were balanced and equally effective, while 1 other said that combination or alternating therapy resulted in more effectiveness than monotherapy in lowering body temperature. body temperature. However, the benefits appear to be small in comparison and may not be clinically relevant.