Hormonal Control of Blood Viscosity.

The hemodynamic milieu differs throughout the vascular tree because of varying vascular geometry and blood velocities. Accordingly, the risk of turbulence, which is dictated by the Reynolds and Dean numbers, also varies. Relatively high blood viscosity is needed to prevent turbulence in the left ventricle and aorta, where high-velocity blood changes direction several times. Low blood viscosity is needed in the capillaries, where erythrocytes pass through vessels with a diameter smaller than their own. In addition, higher blood viscosity is necessary when the cardiac output and peak blood velocity increase as a part of a sympathetic response or anemia, which occurs following significant hemorrhage. Blood viscosity, as reflected in systemic vascular resistance and vascular wall shear stress, is sensed, respectively, by cardiomyocyte stretching in the left ventricle and mechanoreceptors for wall shear stress in the carotid sinus. By controlling blood volume and red blood cell mass, the renin-aldosterone-angiotensin system and the systemic vascular resistance response control the hematocrit, the strongest intrinsic determinant of blood viscosity. These responses provide gross control of blood viscosity. Fine-tuning of blood viscosity in transient conditions is provided by hormonal control of erythrocyte deformability. The short half-life of some of these hormones limits their activity to specific vascular beds. Hormones that modulate blood viscosity include erythropoietin, angiotensin II, brain natriuretic factor, epinephrine, prostacyclin E2, antidiuretic hormone, and nitric oxide.

Comparison of orbital fibroblasts from Graves' ophthalmopathy and healthy control.

Graves' ophthalmopathy (GO) is an extrathyroidal manifestation of Graves' disease, Orbital fibroblasts (OFs) are recognized as key players in GO pathogenesis, involved in orbital inflammation, tissue remodeling, and fibrosis. This study offers a primary exploration of cell behavior and characteristics on OFs from GO (GO-OFs), and compared to OFs from healthy control (HC-OFs). Results reveal that GO-OFs exhibit delayed migration from tissue fragments, while no significant difference in cell proliferation is observed between GO-OFs and HC-OFs. Aberrant expression pattern of surface proteins Thy-1, TSHR, and IGF-1R suggests shared autoantigens and pathways between GO and GD, contributing to inflammation and fibrosis. Investigations into cytokine responses unveil elevated secretion of hyaluronic acid (HA) and prostaglandin E2 (PGE2) in GO-OFs, emphasizing their role in tissue remodeling. These findings deepen our understanding of OFs in GO pathogenesis, offering potential therapeutic avenues.

Maternal Periodontitis Prevalence and its Relationship with Preterm and Low-Birth Weight Infants: A Hospital-Based Research.

Introduction: Overall wellness depends on oral health. Epidemiological, clinical, and laboratory studies have linked periodontitis to some systemic diseases. Pregnancy labor, contractions, and delivery are controlled by prostaglandin (PGE 2) levels rise during pregnancy, and labor begins when a critical threshold is reached. These associations support the underlying cause of maternal periodontal disease. Materials and Methods: In the study, 3,885 pregnant women aged 18-40 had singleton babies. All mother participants were clinically evaluated by the primary investigator. The periodontal disease is defined using a few parameters. Based on that the prevalence rate will be evaluated. Result: The prevalence of preterm babies' mothers affected with periodontitis was 0.5% and low-birth weight babies' mothers affected with periodontitis was 1.6%. So, there was a significant result is there. Conclusion: Periodontal health and preterm LBW newborns are highly associated with periodontitis in research. It may modify preterm birth and LBW risk factors. Thus, dentists detect and treat this sickness early, preventing pregnancy difficulties in sensitive mothers.

Terminalia ferdinandiana Exell. extracts reduce pro-inflammatory cytokine and PGE2 secretion, decrease COX-2 expression and down-regulate cytosolic NF-κB levels.

Based on their high antioxidant capacity and noteworthy phytochemistry, Terminalia ferdinandiana fruit and leaves have attracted considerable recent interest for their therapeutic potential. Whilst those studies have reported a variety of therapeutic properties for the fruit, the anti-inflammatory potential of T. ferdinandiana has been largely neglected and the leaves have been almost completely ignored. This study investigated the immune-modulatory and anti-inflammatory properties of T. ferdinandiana fruit and leaf extracts by evaluating their inhibition of multiple pro- and anti-inflammatory cytokines and chemokines secretion in lipopolysaccharide (LPS)-stimulated and unstimulated RAW 264.7 macrophages using multiplex bead immunoassays and ELISA assays. The methanolic extracts were particularly good immune-modulators, significantly inhibiting the secretion of all the cytokines and chemokines tested. Indeed, the methanolic extracts completely inhibited IL-10, IFN-γ, IL-1ß, IL-6, MCP-1, and MIP-2a secretion, and almost completely inhibited the secretion of TNF-α. In addition, the methanolic T. ferdinandiana extracts also significantly inhibited cytosolic COX-2 levels (by 87-95%) and the synthesis of the PGE2 (by ~ 98%). In contrast, the methanolic extracts stimulated LTB4 secretion by ~ 60-90%, whilst the aqueous extracts significantly inhibited LTB4 secretion (by ~ 27% each). Exposure of RAW 264.7 cells to the methanolic T. ferdinandiana extracts also significantly down-regulated the cytosolic levels of NF-κB by 33-44%, indicating that the immune-modulatory and anti-inflammatory properties of the extracts may be regulated via a decrease in NF-κB transcription pathways. Taken together, these results demonstrate potent anti-inflammatory properties for the extracts and provide insights into their anti-inflammatory mechanisms.

Elevated Prostaglandin E2 Synthesis Is Associated with Clinical and Radiological Disease Severity in Cystic Fibrosis.

Background: Previous studies found high but very variable levels of tetranor-PGEM and PGDM (urine metabolites of prostaglandin (PG) E2 and PGD2, respectively) in persons with cystic fibrosis (pwCF). This study aims to assess the role of cyclooxygenase COX-1 and COX-2 genetic polymorphisms in PG production and of PG metabolites as potential markers of symptoms' severity and imaging findings. Methods: A total of 30 healthy subjects and 103 pwCF were included in this study. Clinical and radiological CF severity was evaluated using clinical scoring methods and chest computed tomography (CT), respectively. Urine metabolites were measured using liquid chromatography/tandem mass spectrometry. Variants in the COX-1 gene (PTGS1 639 C>A, PTGS1 762+14delA and COX-2 gene: PTGS2-899G>C (-765G>C) and PTGS2 (8473T>C) were also analyzed. Results: PGE-M and PGD-M urine concentrations were significantly higher in pwCF than in controls. There were also statistically significant differences between clinically mild and moderate disease and severe disease. Patients with bronchiectasis and/or air trapping had higher PGE-M levels than patients without these complications. The four polymorphisms did not associate with clinical severity, air trapping, bronchiectasis, or urinary PG levels. Conclusions: These results suggest that urinary PG level testing can be used as a biomarker of CF severity. COX genetic polymorphisms are not involved in the variability of PG production.

Optimizing aspirin dose for colorectal cancer patients through deep phenotyping using novel biomarkers of drug action.

Background: Low-dose aspirin's mechanism of action for preventing colorectal cancer (CRC) is still debated, and the optimal dose remains uncertain. We aimed to optimize the aspirin dose for cancer prevention in CRC patients through deep phenotyping using innovative biomarkers for aspirin's action. Methods: We conducted a Phase II, open-label clinical trial in 34 CRC patients of both sexes randomized to receive enteric-coated aspirin 100 mg/d, 100 mg/BID, or 300 mg/d for 3 ± 1 weeks. Biomarkers were evaluated in blood, urine, and colorectal biopsies at baseline and after dosing with aspirin. Novel biomarkers of aspirin action were assessed in platelets and colorectal tissues using liquid chromatography-mass spectrometry to quantify the extent of cyclooxygenase (COX)-1 and COX-2 acetylation at Serine 529 and Serine 516, respectively. Results: All aspirin doses caused comparable % acetylation of platelet COX-1 at Serine 529 associated with similar profound inhibition of platelet-dependent thromboxane (TX)A2 generation ex vivo (serum TXB2) and in vivo (urinary TXM). TXB2 was significantly reduced in CRC tissue by aspirin 300 mg/d and 100 mg/BID, associated with comparable % acetylation of COX-1. Differently, 100 mg/day showed a lower % acetylation of COX-1 in CRC tissue and no significant reduction of TXB2. Prostaglandin (PG)E2 biosynthesis in colorectal tumors and in vivo (urinary PGEM) remained unaffected by any dose of aspirin associated with the variable and low extent of COX-2 acetylation at Serine 516 in tumor tissue. Increased expression of tumor-promoting genes like VIM (vimentin) and TWIST1 (Twist Family BHLH Transcription Factor 1) vs. baseline was detected with 100 mg/d of aspirin but not with the other two higher doses. Conclusion: In CRC patients, aspirin 300 mg/d or 100 mg/BID had comparable antiplatelet effects to aspirin 100 mg/d, indicating similar inhibition of the platelet's contribution to cancer. However, aspirin 300 mg/d and 100 mg/BID can have additional anticancer effects by inhibiting cancerous tissue's TXA2 biosynthesis associated with a restraining impact on tumor-promoting gene expression. EUDRACT number: 2018-002101-65. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03957902.

Exploring PGE2 and LXA4 Levels in Migraine Patients: The Potential of LXA4-Based Therapies.

Neurogenic inflammation plays a significant role in the pathogenesis of migraines. This study aimed to investigate the serum levels of prostaglandin E2 (PGE2), lipoxin A4 (LXA4), and other inflammatory biomarkers (C-reactive protein, fibrinogen) in migraine patients. In total, 53 migraine patients and 53 healthy controls were evaluated. Blood serum samples were collected during both attack and interictal periods and compared with the control group. In both the attack and interictal periods, PGE2 and LXA4 values were significantly lower in migraine patients compared to the control group (p < 0.001). Additionally, PGE2 values during the attack period were significantly higher than those during the interictal period (p = 0.016). Patients experiencing migraine attacks lasting ≥ 12 h had significantly lower serum PGE2 and LXA4 levels compared to those with attacks lasting < 12 h (p = 0.028 and p = 0.009, respectively). In ROC analysis, cut-off values of 332.7 pg/mL for PGE2 and 27.2 ng/mL for LXA4 were determined with 70-80% sensitivity and specificity. In conclusion, PGE2 and LXA4 levels are significantly lower in migraine patients during both interictal and attack periods. Additionally, the levels of LXA4 and PGE2 decrease more with the prolongation of migraine attack duration. Our findings provide a basis for future treatment planning.

Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 Signaling.

NAD+ boosting via nicotinamide riboside (NR) confers anti-inflammatory effects. However, its underlying mechanisms and therapeutic potential remain incompletely defined. Here, we showed that NR increased the expression of CC-chemokine receptor 7 (CCR7) in human M1 macrophages by flow cytometric analysis of cell surface receptors. Consequently, chemokine ligand 19 (CCL19, ligand for CCR7)-induced macrophage migration was enhanced following NR administration. Metabolomics analysis revealed that prostaglandin E2 (PGE2) was increased by NR in human monocytes and in human serum following in vivo NR supplementation. Furthermore, NR-mediated upregulation of macrophage migration through CCL19/CCR7 was dependent on PGE2 synthesis. We also demonstrated that NR upregulated PGE2 synthesis through SIRT3-dependent post-transcriptional regulation of cyclooxygenase 2 (COX-2). The NR/SIRT3/migration axis was further validated using the scratch-test model where NR and SIRT3 promoted more robust migration across a uniformly disrupted macrophage monolayer. Thus, NR-mediated metabolic regulation of macrophage migration and wound healing may have therapeutic potential for the topical management of chronic wound healing.

Prostaglandin Transporter and Dipeptidyl Peptidase-4 as New Pharmacological Targets in the Prevention of Acute Kidney Injury in Diabetes: An In Vitro Study.

The probability of acute kidney injury (AKI) is higher in septic diabetic patients, which is associated with, among other factors, proximal tubular cell (PTC) injury induced by the hypoxic/hyperglycemic/inflammatory microenvironment that surrounds PTCs in these patients. Here, we exposed human PTCs (HK-2 cells) to 1% O2/25 mM glucose/inflammatory cytokines with the aim of studying the role of prostaglandin uptake transporter (PGT) and dipeptidyl peptidase-4 (DPP-4, a target of anti-hyperglycemic agents) as pharmacological targets to prevent AKI in septic diabetic patients. Our model reproduced two pathologically relevant mechanisms: (i) pro-inflammatory PTC activation, as demonstrated by the increased secretion of chemokines IL-8 and MCP-1 and the enhanced expression of DPP-4, intercellular leukocyte adhesion molecule-1 and cyclo-oxygenase-2 (COX-2), the latter resulting in a PGT-dependent increase in intracellular prostaglandin E2 (iPGE2); and (ii) epithelial monolayer injury and the consequent disturbance of paracellular permeability, which was related to cell detachment from collagen IV and the alteration of the cell cytoskeleton. Most of these changes were prevented by the antagonism of PGE2 receptors or the inhibition of COX-2, PGT or DPP-4, and further studies suggested that a COX-2/iPGE2/DPP-4 pathway mediates the pathogenic effects of the hypoxic/hyperglycemic/inflammatory conditions on PTCs. Therefore, inhibitors of PGT or DPP-4 ought to undergo testing as a novel therapeutic avenue to prevent proximal tubular damage in diabetic patients at risk of AKI.

3,4-Methylenedioxymethamphetamine (MDMA) impairs cognitive function during withdrawal via activation of the arachidonic acid cascade in the hippocampus.

BACKGROUND: The recreational drug ±3,4-methylenedioxymethamphetamine (MDMA; also known as "ecstasy") has unusual subjective prosocial and empathogenic effects, and has exhibited potential as an adjunct to psychotherapy in recent years. However, there has been some concern regarding possible neuropsychiatric symptoms, such as cognitive impairment and dependence, emerging after abstinence. Therefore, this study aimed to evaluate the mechanism underlying cognitive impairment during MDMA withdrawal. To achieve this, we focused on the arachidonic acid cascade, which is related to addiction to some abusive drugs. METHODS: A novel object recognition task was used to investigate cognitive function in mice. Furthermore, we quantified prostaglandin E2 during MDMA withdrawal. RESULTS: The recognition index significantly decreased during withdrawal after repeated administration of MDMA (10mg/kg, i.p., once daily for 7 days), but not following co-administration of diclofenac (10mg/kg, i.p.), a cyclooxygenase inhibitor. On day 1, following repeated MDMA treatment, prostaglandin E2 content significantly increased in the hippocampus but not in the prefrontal cortex and striatum. CONCLUSIONS: Our findings indicate that activation of the arachidonic acid cascade at least in the hippocampus is likely involved in the development of recognition memory impairment during MDMA withdrawal. Therefore, co-use of cyclooxygenase inhibitors with MDMA may reduce concerns regarding MDMA-induced impairment of recognition memory.

A highly selective mPGES-1 inhibitor to block abdominal aortic aneurysm progression in the angiotensin mouse model.

Abdominal aortic aneurysm (AAA) is a deadly, permanent ballooning of the aortic artery. Pharmacological and genetic studies have pointed to multiple proteins, including microsomal prostaglandin E2 synthase-1 (mPGES-1), as potentially promising targets. However, it remains unknown whether administration of an mPGES-1 inhibitor can effectively attenuate AAA progression in animal models. There are still no FDA-approved pharmacological treatments for AAA. Current research stresses the importance of both anti-inflammatory drug targets and rigor of translatability. Notably, mPGES-1 is an inducible enzyme responsible for overproduction of prostaglandin E2 (PGE2)-a well-known principal pro-inflammatory prostanoid. Here we demonstrate for the first time that a highly selective mPGES-1 inhibitor (UK4b) can completely block further growth of AAA in the ApoE-/- angiotensin (Ang)II mouse model. Our findings show promise for the use of a mPGES-1 inhibitor like UK4b as interventional treatment of AAA and its potential translation into the clinical setting.

Extracellular acidification attenuates bronchial contraction via an autocrine activation of EP2 receptor: Its diminishment in murine experimental asthma.

PURPOSE: Extracellular acidification is a major component of tissue inflammation, including airway inflammation in asthmatics. However, its physiological/pathophysiological significance in bronchial function is not fully understood. Currently, the functional role of extracellular acidification on bronchial contraction was explored. METHODS: Left main bronchi were isolated from male BALB/c mice. Epithelium-removed tissues were exposed to acidic pH under submaximal contraction induced by 10-5 M acetylcholine in the presence or absence of a COX inhibitor indomethacin (10-6 M). Effects of AH6809 (10-6 M, an EP2 receptor antagonist), BW A868C (10-7 M, a DP receptor antagonist) and CAY10441 (3×10-6 M, an IP receptor antagonist) on the acidification-induced change in tension were determined. The release of prostaglandin E2 (PGE2) from epithelium-denuded tissues in response to acidic pH was assessed using an ELISA. RESULTS: In the bronchi stimulated with acetylcholine, change in the extracellular pH from 7.4 to 6.8 caused a transient augmentation of contraction followed by a sustained relaxing response. The latter inhibitory response was abolished by indomethacin and AH6809 but not by BW A868C or CAY10441. Both indomethacin and AH6809 significantly increased potency and efficacy of acetylcholine at pH 6.8. Stimulation with low pH caused an increase in PGE2 release from epithelium-denuded bronchi. Interestingly, the acidic pH-induced bronchial relaxation was significantly reduced in a murine asthma model that had a bronchial hyperresponsiveness to acetylcholine. CONCLUSION: Taken together, extracellular acidification could inhibit the bronchial contraction via autocrine activation of EP2 receptors. The diminished acidic pH-mediated inhibition of bronchial tone may contribute to excessive bronchoconstriction in inflamed airways such as asthma.

Mating behaviors in ovoviviparous black rockfish (Sebastes schlegelii): molecular function of prostaglandin E2 as both a hormone and pheromone.

Prostaglandins (PGs) are profound hormones in teleost sexual behavior, especially in mating. PGs act as pheromones that affect the olfactory sensory neurons of males, inducing the initiation of a series of mating behaviors. However, the molecular mechanism by which PGs trigger mating behavior in ovoviviparous teleosts is still unclear. In the present study, we employed the ovoviviparous black rockfish (Sebastes schlegelii), an economically important marine species whose reproductive production is limited by incomplete fertilization, as a model species. The results showed that when the dose of PGE2 was higher than 10 nmol/L, a significant (P < 0.05) increase in mating behaviors was observed. Dual-fluorescence in situ hybridization indicated that PGE2 could fire specific neurons in different brain regions and receptor cells in the olfactory sac. After combining with specific neurons in the central nervous system (CNS), a series of genes related to reproduction are activated. The intracerebroventricular administration of PGE2 significantly increased lhb levels (P < 0.05) in both sexes. Moreover, steroidogenesis in gonads was also affected, inducing an increase (P < 0.05) in E2 levels in males and T levels in females. PGE2 levels were also increased significantly (P < 0.05) in both sexes. The present study revealed that PGE2 can activate mating behavior in black rockfish in both hormone and pheromone pathways, leading to variations in sex steroid levels and activation of reproductive behaviors. Our results provide not only novel insight into the onset of mating behaviors in ovoviviparous teleosts but also solutions for the incomplete fertilization caused by natural mating in cage aquaculture. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00214-w.

Effect of 2% meloxicam injection in Holstein dairy cows on acute clinical mastitis without systemic symptoms.

This study aimed the efficacy of meloxicam (MX) in treating acute clinical mastitis (ACM) without systemic symptoms in Holstein cows by studying improvement in udder pain, changes in prostaglandin E2(PGE2) and bradykinin (BK) levels in the milk, and milk yield (MY) after healing. Forty-two cows with ACM were randomly assigned to the MX treatment group (T group; n=21) and the control group (C group; n=21). At onset of illness (day 0), the T group received a 0.5 mg/kg subcutaneous (SC) injection of MX whereas the C group received 15 mL SC of saline solution as a placebo. Udder tenderness (UT) was measured, and milk samples were collected on days 0-3. There was little change in the MY of the T group before and after healing, whereas MY in the C group was significantly lower than after healing. UT on day 3 in the T group was significantly lower than that in the C group. PGE2 levels significantly decreased from day 0 to day 3 in both groups. A significant negative correlation between PGE2 and linear score was observed on day 1 in the T group, but not in the C group. In ACM without systemic symptoms, the administration MX may be useful for restoring MY and reducing udder pain after healing.

EP2 and EP4 blockade prevents tumor-induced suppressive features in human monocytic myeloid-derived suppressor cells.

Tumors educate their environment to prime the occurrence of suppressive cell subsets, which enable tumor evasion and favors tumor progression. Among these, there are the myeloid-derived suppressor cells (MDSCs), their presence being associated with the poor clinical outcome of cancer patients. Tumor-derived prostaglandin E2 (PGE2) is known to mediate MDSC differentiation and the acquisition of pro-tumor features. In myeloid cells, PGE2 signaling is mediated via E-prostanoid receptor type 2 (EP2) and EP4. Although the suppressive role of PGE2 is well established in MDSCs, the role of EP2/4 on human MDSCs or whether EP2/4 modulation can prevent MDSCs suppressive features upon exposure to tumor-derived PGE2 is poorly defined. In this study, using an in vitro model of human monocytic-MDSCs (M-MDSCs) we demonstrate that EP2 and EP4 signaling contribute to the induction of a pro-tumor phenotype and function on M-MDSCs. PGE2 signaling via EP2 and EP4 boosted M-MDSC ability to suppress T and NK cell responses. Combined EP2/4 blockade on M-MDSCs during PGE2 exposure prevented the occurrence of these suppressive features. Additionally, EP2/4 blockade attenuated the suppressive phenotype of M-MDSCs in a 3D coculture with colorectal cancer patient-derived organoids. Together, these results identify the role of tumor-derived PGE2 signaling via EP2 and EP4 in this human M-MDSC model, supporting the therapeutic value of targeting PGE2-EP2/4 axis in M-MDSCs to alleviate immunosuppression and facilitate the development of anti-tumor immunity.

Prostaglandin E2 may clinically alleviate dry eye disease by inducing Th17 cell differentiation.

Dry eye (DE) is a multifactorial ocular surface disease characterised by an imbalance in tear homeostasis. The pathogenesis of DE is complex and related to environmental, immunological (e.g., T helper 17 cells) and other factors. However, the DE disease pathogenesis remains unclear, thereby affecting its clinical treatment. This study aimed to explore the mechanism through which prostaglandin E2 (PGE2) affects DE inflammation by regulating Th17. The DE mouse model was established through subcutaneous injection of scopolamine hydrobromide. The tear secretion test and break-up time (BUT) method were used to detect tear secretion and tear film BUT, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of PGE2, interleukin (IL)-17, IL-6 and tumour necrosis factor (TNF-α) in tear fluid and those of PGE2 and IL-17 in the serum. RT-qPCR and western blotting were used to test the mRNA and protein expression levels of IL-17 and retinoid-related orphan receptor-γt (RORγt). PGE2 was highly expressed in the DE mouse model. The mRNA and protein levels of IL-17 and the key Th17 transcription factor RORγt were increased in tissues of the DE mice. Moreover, PGE2 promoted tear secretion, reduced the BUT, increased the IL-17 concentration in tears and increased the Th17 cell proportion in DE, whereas the PGE2 receptor inhibitor AH6809 reversed the effects of PGE2 on tear secretion, BUT, and the Th17 cell proportion in draining lymph node (DLN) cells. Taken together, the study findings indicate that PGE2 could induce DE-related symptoms by promoting Th17 differentiation.

Melanoxetin: A Hydroxylated Flavonoid Attenuates Oxidative Stress and Modulates Insulin Resistance and Glycation Pathways in an Animal Model of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (DM) continues to escalate, necessitating innovative therapeutic approaches that target distinct pathways and address DM complications. Flavonoids have been shown to possess several pharmacological activities that are important for DM. This study aimed to evaluate the in vivo effects of the flavonoid melanoxetin using Goto-Kakizaki rats. Over a period of 14 days, melanoxetin was administered subcutaneously to investigate its antioxidant, anti-inflammatory, and antidiabetic properties. The results show that melanoxetin reduced insulin resistance in adipose tissue by targeting protein tyrosine phosphatase 1B. Additionally, melanoxetin counteracted oxidative stress by reducing nitrotyrosine levels and modulating superoxide dismutase 1 and hemeoxygenase in adipose tissue and decreasing methylglyoxal-derived hydroimidazolone (MG-H1), a key advanced glycation end product (AGE) implicated in DM-related complications. Moreover, the glyoxalase 1 expression decreased in both the liver and the heart, correlating with reduced AGE levels, particularly MG-H1 in the heart. Melanoxetin also demonstrated anti-inflammatory effects by reducing serum prostaglandin E2 levels, and increasing the antioxidant status of the aorta wall through enhanced acetylcholine-dependent relaxation in the presence of ascorbic acid. These findings provide valuable insights into melanoxetin's therapeutic potential in targeting multiple pathways involved in type 2 DM, particularly in mitigating oxidative stress and glycation.

The curative efficacy of auricular comprehensive therapy on menstrual migraine and its effect on serum prostaglandin. / è€³ç©´ç»¼åˆç–—æ³•æ²»ç–—æœˆç»æ€§åå¤´ç—›æ‚£è€ ä¸´åºŠç–—æ•ˆåŠå¯¹è¡€æ¸ å‰åˆ—è ºç´ çš„å½±å“.

OBJECTIVES: To observe the curative efficacy of auricular comprehensive therapy on menstrual migraine(MM) and its effect on serum prostaglandin F2α(PGF2α), prostaglandin E2(PGE2) contents and ratio, so as to explore its possible mechanism. METHODS: A total of 66 patients with MM of liver-fire syndrome were randomly divided into observation group (33 cases, 2 cases dropped off) and control group (33 cases, 2 cases dropped off), and 20 healthy women were included in the normal group. Patients in the control group were given flunarizine hydrochloride capsules orally, twice a day, for 3 consecutive weeks. Patients in the observation group were treated with auricular comprehensive therapy, starting 2-5 days before menstrual cramps, once a week, for a total of 3 weeks. The visual analogue scale (VAS) and migraine score were evaluated before and after treatment, and follow-up for 1 and 2 menstrual cycles. Serum PGF2α and PGE2 contents were measured before and after treatment, and the PGF2α/PGE2 ratio was calculated. The clinical effective rates in the two groups were calculated. RESULTS: After treatment and follow-up for 1 and 2 menstrual cycles, the VAS scores, headache degree, the frequency and duration of headache attacks, as well as accompanying symptoms of the observation and control groups were lower than those before treatment(P<0.05), and those of the observation group was lower than those of the control group(P<0.05). Before treatment, the PGF2α contents in the observation and control group were significantly higher(P<0.05), while the PGE2 contents lower(P<0.05) and PGF2α/PGE2 ratio higher(P<0.05) than those in the normal group. After treatment, the serum PGF2α contents in the observation and control group were significantly reduced compared with which before treatment(P<0.05), and were lower in the observation group than that in the control group (P<0.05). The serum PGE2 contents in the observation and control groups were significantly increased after treatment compared with which before treatment(P<0.05), with the contents in the observation group higher than that in the control group(P<0.05). The serum PGF2α/PGE2 ratio in the observation and control group was significantly reduced after treatment compared with which before treatment(P<0.05), with the control group higher than the normal group(P<0.05), and the observation group lower than the control group(P<0.05). The clinical effective rate of the observation group was 93.5% (29/31), and that of the control group was 77.4% (24/31). The effective rate of the observation group was significantly higher than that of the control group(P<0.05). CONCLUSIONS: The curative efficacy of auricular comprehensive therapy on MM with liver-fire syndrome is significantly better than that of oral flunarizine hydrochloride capsules, especially in relieving hea-daches, reducing the frequency and duration of headache attacks, as well as accompanying symptoms. Its mechanism may be related to regulating the abnormal PGF2α and PGE2 contents of patients and reducing the ratio of PGF2α/PGE2.

Oxytocin and vaginal dinoprostone in labor induction: A systematic review and meta-analysis.

BACKGROUND: The comparison between prostaglandin E2 (PGE2) and oxytocin and for induction of labor (IOL) remains controversial. OBJECTIVE: The present study aimed to determine the safety and efficacy of these two agents in IOL. SEARCH STRATEGY: PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. from the establishment of the database to April 23, 2023. SELECTION CRITERIA: A search was conducted with keywords "labor, induction, prostaglandin E2/PGE2/dinoprostone, and oxytocin". Only randomized clinical trials comparing oxytocin and vaginal dinoprostone in women who were at least late preterm (gestational age [GA] ≥34 weeks), singleton pregnant, and had intact membranes were enrolled for further meta-analysis. DATA COLLECTION AND ANALYSIS: We conducted both a descriptive analysis and a meta-analysis. In the meta-analysis, we utilized the Mantel-Haenszel random effects model to analyze dichotomous data, employing the relative risk (RR) as the effect measure along with 95% confidence intervals (CIs). The study quality was evaluated using Cochrane Collaboration's risk of bias assessment tool (RoB 2). A random-effects model was applied for the meta-analysis. MAIN RESULTS: After screening 3303 articles from five databases, a total of nine randomized controlled studies composed of 1071 patients were included. Our analysis included 534 patients in the PGE2 group and 537 patients in the oxytocin group. The pooled estimate of vaginal deliveries following PGE2 induction stood at 84.2%, while after oxytocin induction, it was 79.8%. The meta-analysis showed no statistical difference between the two groups in terms of the rate of vaginal delivery (pooled RR, 1.05; 95% CI: 0.95-1.16; P value for Q, 0.001; I2 , 71.14%), cesarean section (pooled RR, 0.84; 95% CI: 0.52-1.35; P value for Q, 0.007; I2 , 61.69%) and induction-delivery interval (pooled standard mean difference, 0.09; 95% CI: -0.67 to 0.85; P value for Q, 0.000; I2 , 96.45%). Since the results for fetal distress and uterine hyperstimulation were consistent across all enrolled studies, no further meta-analysis was conducted. CONCLUSIONS: When amalgamating the available literature, it implies that oxytocin was found to have similar effects as PGE2 on delivery outcomes and safety concerns in pregnant women with GA ≥36 weeks. Although the uterine cervix was unfavorable, both low and high doses of oxytocin were feasible for IOL.

Urinary Prostaglandin E2 Excretion and the Risk of Cardiovascular and Kidney Disease.

BACKGROUND: Inhibition of prostaglandin synthesis by nonsteroidal anti-inflammatory drugs is associated with cardiovascular mortality and kidney disease. This study hypothesizes that urinary prostaglandin E2 (PGE2) and PGE2 metabolite (PGEM) excretions are markers of cardiovascular and kidney health, because they reflect both systemic and kidney-derived PGE2 production. METHODS AND RESULTS: PGE2 and PGEM were measured in spot urine samples from 2291 participants (≥55 years old) of the population-based Rotterdam Study. Urinary PGE2 and PGEM excretions were analyzed using linear regression analyses to identify cross-sectional associations with cardiovascular risk factors and baseline estimated glomerular filtration rate (eGFR). Longitudinal associations with cardiovascular mortality and kidney outcomes (eGFR <60 or <45 mL/min per 1.73 m2 and the composite outcome 40% eGFR loss or kidney failure) were assessed with Cox regression. Urinary PGE2 and PGEM excretions were higher with increasing age, lower eGFR, smoking, diabetes, and albuminuria. A 2-fold higher urinary PGE2 and PGEM excretion was associated with a higher risk of cardiovascular mortality (28 825 patient-years; 160 events; PGE2 hazard ratio [HR], 1.27, [95% CI, 1.06-1.54]; PGEM HR, 1.36 [95% CI, 1.10-1.67]). Higher PGE2 excretions were also associated with a higher risk of incident eGFR <60 mL/min per 1.73 m2 (31 530 person-years; 691 events; HR, 1.13 [95% CI, 1.02-1.25]) with similar HRs for the other kidney outcomes. CONCLUSIONS: Urinary PGE2 and PGEM excretions are novel markers for the presence and progression of cardiovascular and kidney disease. Future studies should address whether these associations are causal and can be targeted to improve cardiovascular and kidney outcomes.