Prostaglandin E2 Levels Research Articles

Inhibitory Effect of (2S)‐Pinocembrin From Goniothalamus macrophyllus on the Prostaglandin E2 Production in Macrophage Cell Lines

Pinocembrin (PCB), a flavonoid known for its anti‐inflammatory properties, has been approved for various clinical trial applications. To evaluate deeper into the anti‐inflammatory potential of the specific enantiomer of natural PCB, we conducted the first investigation into the efficacy of the pure enantiomer (2S)‐PCB in modulating inflammatory mediators induced by lipopolysaccharide (LPS) in both murine RAW 264.7 and human U937 macrophage cell lines. This particular compound was isolated from Goniothalamus macrophyllus (Annonaceae), a native plant of Indonesia. This plant has been used traditionally as an herbal medicine to alleviate inflammation. (2S)‐PCB was isolated from the stem bark of G. macrophyllus by defatting with n‐hexane followed by maceration with methanol. Purification was performed using several chromatographic techniques. The absolute configuration was determined using electronic circular dichroism (ECD) spectroscopy. This compound was then tested for its inhibitory activity on prostaglandin E2 (PGE2) and subjected to docking simulations. The results indicated that (2S)‐PCB significantly suppressed the production of PGE2 induced by LPS in both RAW 264.7 and U937 cell lines. The docking simulations revealed that (2S)‐PCB reduced PGE2 levels by suppressing mitogen‐activated protein kinase (MAPK) activation through inhibiting p38 and extracellular signal‐regulated kinases (ERK). These findings suggest that the compound may prevent worsening of septic shock caused by bacterial infection.

Реконструктивная локальная инъекционная терапия

The article discusses the treatment of osteoarthritis (OA) as the most common joint disease. The recommendations from professional associations for the patient management in OA using hyaluronic acid (HA) preparations differ somewhat depending on the affected joint, although they generally indicate positive effects of their use. Studies have shown the HA participation in the phagocytosis reduction, as well as in lowering the levels of prostaglandins, fibronectin, cAMP and a number of other anti-inflammatory effects. There is also a hypothesis that HA can prevent the release of arachidonic acid, block nociceptors and reduce the bradykinin formation, as well as it has chondroprotective properties. At the same time, total joint replacement is considered optimal (which has proven itself to be an effective and safe type of surgery) during the OA progression, the preservation of severe pain and loss of joint function, and the inefficacy of conservative treatment. The authors draw attention to the most common complication that occurs during total joint replacement — contralateral limb pain, and explain the mechanisms of its progression. They also present their case follow-ups of patients after total joint replacement with the development of synovitis in the contralateral hip joint and synovitis in combination with ligamentitis in the contralateral knee joint. Besides, the article highlights the clinical picture patterns and the methods of reconstructive local injection therapy with HA. KEYWORDS: osteoarthritis, knee joint, hip joint, hyaluronic acid, total joint replacement, contralateral limb pain, intra-articular injection, periarticular injection. FOR CITATION: Filatova Yu.S., Solovyov I.N., Solovyov E.I. Reconstructive local injection therapy. Russian Medical Inquiry. 2024;8(4):208– 214 (in Russ.). DOI: 10.32364/2587-6821-2024-8-4-4.

The Effect of Abdominal Stretching, Yoga, and Dysmenorrhea Exercises on Prostaglandin Levels and Pain

Introduction: Dysmenorrhea, or pain during menstruation, affects a high percentage of women of reproductive age. It can disrupt learning activities at school, cause a lack of concentration, and lead to frequent absences, ultimately decreasing the quality of life for young women. The purpose of this study was to analyze the effect of abdominal stretching, yoga, and dysmenorrhea exercises on prostaglandin levels and pain in school-age adolescents. Method: A quasi-experimental study with an experimental laboratory design was used, with pretest and posttest control groups. The sampling technique used was probability sampling with simple random sampling of 32 female students divided into four groups, with three groups receiving abdominal stretching, yoga therapy, and dysmenorrhea exercises, respectively, and one group serving as the control group. Data was analyzed using one-way ANOVA and the Kruskal-Wallis test. Results: The average prostaglandin levels after treatment were highest in the abdominal stretching group at 31.7 pg/mL and lowest in the dysmenorrhea group at 19.0 pg/mL. The difference in prostaglandin levels was highest in the dysmenorrhea exercise group at 42.5 pg/mL and lowest in the control group at 14.4 pg/mL. Most participants who experienced moderate pain before and after the intervention generally complained of mild pain. Conclusion: The study found a significant effect of abdominal stretching therapy, yoga therapy, and dysmenorrhea exercises on prostaglandin levels and pain. Dysmenorrhea exercises were found to be the most effective therapy in reducing prostaglandin levels and dysmenorrhea pain, compared to abdominal stretching and yoga therapy.

Efficacy and safety of pulsed radiofrequency combined with gabapentin in the treatment of acute herpetic neuralgia

Objective: To explore the clinical efficacy and safety of pulsed radiofrequency (PRF) combined with gabapentin in the treatment of acute herpetic neuralgia (AHN). Methods: A total of 123 AHN patients were retrospectively selected in Henan Provincial People's Hospital from November 2019 to July 2022, who were divided into two groups based on treatment methods: control group (treated with gabapentin, n=61) and study group (treated with gabapentin and PRF, n=62). The visual analog scale (VAS) was utilized for pain severity assessment and the self-rating scale for sleep (SRSS) was utilized for sleep quality evaluation. The differences in serum levels of interleukin (IL)-10, chemokine ligand 10 (CXCL-10), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), IL-2 and IL-6 before and after treatment were compared between the two groups. The overall treatment effectiveness and the occurrence rates of postherpetic neuralgia and adverse reactions were evaluated in both groups. Results: Among the study group patients, 28 were male and 34 were female, and the age was (62.8±8.5) years. Among the control group patients, 35 were male and 26 were female, and the age was (64.0±7.8) years. The VAS scores of the study group before and after treatment were 7.96±1.33 and 1.52±0.60, respectively, while the control group were 7.68±1.52 and 2.70±0.64. The SRSS scores before and after treatment in the study group were 31.74±5.90 and 12.06±2.81, respectively, while those in the control group were 33.10±5.54 and 14.14±2.96, respectively. Before treatment, there were no statistically differences of the VAS scores and SRSS scores in both groups (all P>0.05). After treatment, the VAS scores and SRSS scores in both groups decreased compared with before treatment (all P<0.05), the study group's VAS scores and SRSS scores were lower than those in the control group (all P<0.05). Before treatment, there were no statistically differences of the serum levels of IL-10, CXCL-10, PGE2, COX-2, IL-2 and IL-6 in both groups (all P>0.05). After treatment, the serum levels of IL-10, CXCL-10, PGE2, COX-2 and IL-6 in both groups decreased compared with before treatment, while the IL-2 level increased. Additionally, the study group had lower serum levels of IL-10, PGE2, COX-2 and IL-6 compared with the control group (all P<0.05). After treatment, the study group had 35 cases of cure, 26 cases of effectiveness, and 1 case of ineffectiveness, while the control group had 22 cases of cure, 31 cases of effectiveness, and 8 cases of ineffectiveness. The overall treatment efficacy of the study group was better than that of the control group (P=0.012). The incidence of postherpetic neuralgia in the study group after treatment was 16.1% (10/62), which was lower than that in the control group, which was 37.7% (23/61) (P<0.05). There were no statistically differences of the occurrence rates of adverse reactions in both groups (all P>0.05). Conclusion: Combining PRF with gabapentin for the treatment of AHN demonstrates better overall efficacy and safety, which can more effectively alleviate pain, improve sleep, and reduce inflammatory cytokine levels.

Tissue lipidomic profiling supports a mechanistic role of the prostaglandin E2 pathway for albuminuria development in glomerular hyperfiltration.

Background: Glomerular hyperfiltration (GH) is an important mechanism in the development of albuminuria in hypertension. The Munich Wistar Frömter (MWF) rat is a non-diabetic model of chronic kidney disease (CKD) with GH due to inherited low nephron number resulting in spontaneous albuminuria and podocyte injury. In MWF rats, we identified prostaglandin (PG) E2 (PGE2) signaling as a potential causative mechanism of albuminuria in GH. Method: For evaluation of the renal PGE2 metabolic pathway, time-course lipidomic analysis of PGE2 and its downstream metabolites 15-keto-PGE2 and 13-14-dihydro-15-keto-PGE2 was conducted in urine, plasma and kidney tissues of MWF rats and albuminuria-resistant spontaneously hypertensive rats (SHR) by liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Results: Lipidomic analysis revealed no dysregulation of plasma PGs over the time course of albuminuria development, while glomerular levels of PGE2 and 15-keto-PGE2 were significantly elevated in MWF compared to albuminuria-resistant SHR. Overall, averaged PGE2 levels in glomeruli were up to ×150 higher than the corresponding 15-keto-PGE2 levels. Glomerular metabolic ratios of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) were significantly lower, while metabolic ratios of prostaglandin reductases (PTGRs) were significantly higher in MWF rats with manifested albuminuria compared to SHR, respectively. Conclusion: Our data reveal glomerular dysregulation of the PGE2 metabolism in the development of albuminuria in GH, resulting at least partly from reduced PGE2 degradation. This study provides first insights into dynamic changes of the PGE2 pathway that support a role of glomerular PGE2 metabolism and signaling for early albuminuria manifestation in GH.

Potential inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced inflammation, hyperproliferation, and hyperplasiogenic responses by celecoxib in mouse skin

Purpose Skin exposure to noxious agents leads to cutaneous lesion marked by an increase in inflammation, cellular proliferation, and hyperplasiogenic reactions. Studies have demonstrated that these damages breach the skin integrity resulting in the aetiology of various cutaneous disorders like atopic dermatitis, eczema, psoriasis, and development of non-melanoma skin cancer. Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, is an effective treatment for a variety of inflammatory diseases. Its importance in the therapy of skin problems, however, remains under appreciated. Methods We tested efficacy of topically applied celecoxib in mitigating skin inflammation, cellular proliferation, and hyperplasia induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in Swiss albino mice. Results Celecoxib (5 and 10 μmol) markedly reduced TPA (10 nmol) induced prostaglandin E2 (PGE2) production, oedema formation, myeloperoxidase (MPO) activity, and levels of pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). It also resulted in a considerable decrease in ornithine decarboxylase (ODC) activity and the incorporation of [3H]-thymidine into DNA. In addition, there was a significant reduction in histoarchitectural abnormalities such as epidermal thickness, number of epidermal cell layers, neutrophil infiltration, intercellular oedema, and vasodilation. Conclusion Our results demonstrate that topical celecoxib can reduce the inflammation, hyperproliferation, and hyperplasiogenic events of skin insults suggesting that it may prove to be a valuable management option for cutaneous lesion and associated illnesses such as atopic dermatitis, eczema, and psoriasis, as well as the emergence of non-melanoma cancer.

Modulation of thermal stress response by prostaglandins in gills of the blue mussel Mytilus edulis

Mytilus edulis has experienced massive mortality events associated with thermal stress that have been documented in wild as well as cultivated organisms, since this species is traditionally farmed in intertidal areas that are exposed to temperature variations. The stress responses linked to changes in temperature are modulated by prostaglandins (PG), which induce apoptosis, synthesis of heat shock proteins and antioxidant enzymes, among others. PG are mainly synthesized from arachidonic (ARA), eicosapentaenoic (EPA) and docosahexaenoic (DHA), but PG-like compounds can be produced through non-enzymatic oxidation of fatty acids in response to increased reactive oxygen species (ROS). In this study, we applied acute (a single temperature increase of 13 °C, from 12 °C to 25 °C) or chronic (cyclical temperature increases and decreases of 13 °C for eight days) thermal stress to mussels fed a microalga mix of Nannochloropsis oculata and Pavlova lutheri. The response was quantified by measuring PG produced enzymatically by cyclooxygenase (COX) from ARA, EPA, and DHA (PGE2, PGE3, 13-HDHA, respectively), non-enzymatic PG (13,14-dihydro-15-keto-PGE2 PGF3α and 8-isoprostane). PGE2, PGE3, and 13-HDHA levels were higher in the gills of mussels exposed to acute stress compared to chronic stress while 3,14-dihydro-15-keto-PGE2 showed no significant differences as a result of chronic or acute stress. PGF3α had lower levels in mussels exposed to chronic stress compared to those under acute stress. In contrast, 8-isoprostane was significantly higher in mussels exposed to chronic stress compared to acute stress. Mussels exposed to acute stress showed an increase in hemocyte infiltration in the gills, while those exposed to chronic stress showed a decrease in gill filament width compared to mussels submitted to acute stress; both effects are associated with PG modulation. These findings suggest that acute and chronic stressors have distinct effects on lipid composition, prostaglandin levels, and gill filament morphology, highlighting potential adaptations or responses to different stress conditions. Understanding the mechanisms by which PG and PG-like compounds modulate the thermal stress response in mussels will contribute to the understanding of climate change impacts on bivalves and the possible adaptation processes involved.

Urine biomarker could be a useful tool for differential diagnosis of a lower urinary tract dysfunction.

A precision diagnosis of lower urinary tract dysfunctions (LUTD) such as bladder outlet obstruction, detrusor overactivity (DO), interstitial cystitis/bladder pain syndrome (IC/BPS), dysfunctional voiding (DV), or detrusor underactivity (DU) needs invasive videourodynamic study. Exploring non-invasive tools to help screening LUTD is necessary for clinicians in their daily practice. This article reviews recently clinical studies of using urinary inflammatory proteins and oxidative stress biomarkers in the identification of specific LUTD among men and women with lower urinary tract symptoms (LUTS). Some important findings have been reported: (1) Using urine chemokines CXCL-1 and interleukin-8 (IL-8), we may discriminate overactive bladder (OAB) symptoms in women between DO and urinary tract infection. (2) Urinary levels of oxidative stress biomarkers such as 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane have a potential being used as a tool to identify women with mixed DO and stress urinary incontinence. (3) Urine levels of total antioxidant capacity (TAC), and prostaglandin E2 (PGE2) are positively correlated with voiding detrusor pressure in patients with DU. (4) Urine levels of brain-derived neurotrophic factor (BDNF) and PGE2 were significantly higher in the DU patients with detrusor function recovery. (5) Women with DV had higher urinary levels of tumor necrosis factor-alpha (TNF-α) and 8-OHdG, and urinary IL-2 level was significantly lower. (6) Urine level of 8-isoprostane was higher in the patients with idiopathic DO and neurogenic DO. (7) Higher urine cytokine levels of monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted (RANTES), CXCL-10, IL-7, and eotaxin-1 in patients with IC/BPS than controls. (8) The urine levels of IL-8, CXCL-10, BDNF, IL-6, and RANTES were significantly higher in patients with Hunner's IC than non-Hunner's IC. (9) Male patients with IC/BPS had a significantly higher level of eotaxin, MCP-1, TNF-α, 8-OHdG, and TAC. Combining a higher eotaxin and a higher TNF-α can provide a satisfactory diagnostic value in discriminating IC/BPS from other LUTD in men. These studies provide evidence that measurement of cluster of urine biomarkers could be used as a diagnostic tool to differentiate different LUTD in patients with similar LUTS.

Hepatic oxylipin profiles in mouse models of Wilson disease: New insights into early hepatic manifestations

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.

Plasma cytokines profile in patients with Alzheimer’s and Parkinson’s Disease: a comparative study in terms of inflammation

Background Neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease inflict economic and health burdens on societies. Alzheimer’s disease (AD), the most prevalent form of dementia, is accompanied by progressive degradation of memory, decision-making, and judgment. Parkinson’s disease (PD) is characterized by resting tremor, rigidity, bradykinesia, and loss of balance. Extensive research has pinpointed inflammation as a cause of the onset and progression of both diseases. However, it has not been confirmed which one is more formidable in terms of inflammation. Methods To assess the extent of inflammation that is implicated in AD and PD and answer the question of which one is more inflammatory, serum levels of inflammatory biomarkers, including cytokines, chemokines, and prostaglandin E2 (PEG2), were measured in AD and PD patients as well as a healthy group. Results Our results showed a significant increase in IL-1α, IL-1β, IL-4, IL-6, IL-10, IL-12p70, IP-10, MCP-1, PEG2, and TNF-α in AD and PD patients compared with the control. Interestingly, IFN-γ did not manifest any significant difference in AD or PD patients compared with the control. Conclusion As a hallmark of our results, it could be inferred that inflammation, as the underlying etiological cause, plays a more crucial role in PD compared with AD. Based on our results, it is proposed that anti-inflammatory remedies would be putatively more effective in PD rather than AD.

Peony Pollen Protects against Primary Dysmenorrhea in Mice by Inhibiting Inflammatory Response and Regulating the COX2/PGE2 Pathway.

Peony pollen contains multiple nutrients and components and has been used as a traditional Chinese medicine with a long history, but the effect of the treatment of primary dysmenorrhea remains to be clarified. The aim of this study is to investigate the therapeutic effect of peony pollen on primary dysmenorrhea mice and the potential mechanism. A uterus contraction model in vitro and primary dysmenorrhea mice were used to evaluate the treatment effect of peony pollen on primary dysmenorrhea. The primary dysmenorrhea mice were treated with 62.5 mg/kg, 125 mg/kg, or 250 mg/kg of peony pollen, and the writhing response, latency period, histopathological changes in the uterus, prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) levels, and infiltration of neutrophils and macrophages were investigated. Protein expression of interleukin 1 β (IL-1β), interleukin 6 (IL-6), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cyclooxygenase-2 (COX-2), microsomal prostaglandin-E synthase 1 (mPGEs-1), BCL2-Associated X (Bax), B-cell lymphoma-2 (BCL-2), caspase-3, and cleaved caspase-3 were detected by Western blot, and the oxidative stress related marker malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and reactive oxygen species (ROS) were evaluated. Peony pollen could attenuate spontaneous or oxytocin-induced uterus contractions in vitro. Moreover, peony pollen decreased the writhing times, prolonged the writhing latency, and reduced the pathological damage of uterine tissues. Furthermore, the inflammatory cell infiltration and the protein expression of IL-1β, IL-6, and NLRP3 were decreased. The COX-2/PGE2 pathway was inhibited; oxidative stress and apoptosis in the uterus also improved in the uterus of primary dysmenorrhea mice. Peony pollen exerts a positive effect on primary dysmenorrhea by inhibiting the inflammatory response and modulating oxidative stress and apoptosis by regulating the COX-2/PGE2 pathway.

Pyrogenic and inflammatory mediators are produced by polarized M1 and M2 macrophages activated with D-dimer and SARS-CoV-2 spike immune complexes

Lung macrophages are the first line of defense against invading respiratory pathogens including SARS-CoV-2, yet activation of macrophage in the lungs can lead to hyperinflammatory immune response seen in severe COVID-19. Here we used human M1 and M2 polarized macrophages as a surrogate model of inflammatory and regulatory macrophages and explored whether immune complexes (IC) containing spike-specific IgG can trigger aberrant cytokine responses in macrophages in the lungs and associated lymph nodes. We show that IC of SARS-CoV-2 recombinant S protein coated with spike-specific monoclonal antibody induced production of Prostaglandin E2 (PGE2) in non-polarized (M0) and in M1 and M2-type polarized human macrophages only in the presence of D-dimer (DD), a fibrinogen degradation product, associated with coagulopathy in COVID-19. Importantly, an increase in PGE2 was also observed in macrophages activated with DD and IC of SARS-CoV-2 pseudovirions coated with plasma from hospitalized COVID-19 patients but not from healthy subjects. Overall, the levels of PGE2 in macrophages activated with DD and IC were as follows: M1≫M2>M0 and correlated with the levels of spike binding antibodies and not with neutralizing antibody titers. All three macrophage subsets produced similar levels of IL-6 following activation with DD+IC, however TNFα, IL-1β, and IL-10 cytokines were produced by M2 macrophages only. Our study suggests that high titers of spike or virion containing IC in the presence of coagulation byproducts (DD) can promote inflammatory response in macrophages in the lungs and associated lymph nodes and contribute to severe COVID-19.

Effect of psychosocial stress during pregnancy against prostaglandin hormone levels in maternity

Stress is a mental health problem in pregnancy and affects the birthing process of breastfeeding. Stress can affect physiological processes in the body, including hormones in labor. This study evaluated the effects of stress during pregnancy on prostaglandin hormone levels in the mother during maternity. This research is an observational study using a prospective cohort approach. The number of samples in this study was 121 samples. Stress change data were analyzed using the Wilcoxon rank test and 1-way test ANOVA. The results showed there was a change in stress from first trimester to second trimester there were 23 respondents who experienced increased stress (p=0.000), second trimester to third trimester there were 102 respondents who experienced increased stress (p=0.000), and first trimester to third trimester there were 78 respondents who experienced increased stress (p=0.000). There were different prostaglandin levels based on stress levels. The mother's high stress that elevated prostaglandin levels. Stress can positively or negatively impact the processes in the mother's body, including in the delivery process effects of stress, especially on uterine contractions. Therefore, health workers can provide care by paying attention to the psychological aspects of the mother because psychological conditions can affect the processes in the mother's body.

Gintonin Alleviates HCl/Ethanol- and Indomethacin-Induced Gastric Ulcers in Mice.

Gintonin, newly extracted from ginseng, is a glycoprotein that acts as an exogenous lysophosphatidic acid (LPA) receptor ligand. This study aimed to demonstrate the in vivo preventive effects of gintonin on gastric damage. ICR mice were randomly assigned to five groups: a normal group (received saline, 0.1 mL/10 g, p.o.); a control group (administered 0.3 M HCl/ethanol, 0.1 mL/10 g, p.o.) or indomethacin (30 mg/kg, p.o.); gintonin at two different doses (50 mg/kg or 100 mg/kg, p.o.) with either 0.3 M HCl/ethanol or indomethacin; and a positive control (Ranitidine, 40 mg/kg, p.o.). After gastric ulcer induction, the gastric tissue was examined to calculate the ulcer index. The expression of gastric damage markers, such as tumor necrosis factor (TNF)-α, cyclooxygenase 2 (COX-2), and LPA2 and LPA5 receptors, were measured by Western blotting. Interleukin-6 (IL-6) and prostaglandin E2 (PGE2) levels were measured by enzyme-linked immunosorbent assay. The platelet endothelial cell adhesion molecule (PECAM-1), Evans blue, and occludin levels in gastric tissues were measured using immunofluorescence analysis. Both HCl/ethanol- and indomethacin-induced gastric ulcers showed increased TNF-α, IL-6, Evans blue permeation, and PECAM-1, and decreased COX-2, PGE2, occludin, and LPA5 receptor expression levels. However, oral administration of gintonin alleviated the gastric ulcer index induced by HCl/ethanol and indomethacin in a dose-dependent manner. Gintonin suppressed TNF-α and IL-6 expression, but increased COX-2 expression and PGE2 levels in mouse gastric tissues. Gintonin intake also increased LPA5 receptor expression in mouse gastric tissues. These results indicate that gintonin can play a role in gastric protection against gastric damage induced by HCl/ethanol or indomethacin.

TT-10 may attenuate ibuprofen-induced ovarian injury in mice by activating COX2-PGE2 and inhibiting Hippo pathway

Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug that has been found in recent years to cause ovarian damage. The aim of this study is to explore the molecular mechanisms of IBU damage to the ovary and drugs to combat it. We established in vivo (IBU doses of 50, 100 and 200 mg/kg-day) and in vitro (IBU concentrations of 50, 100 and 200 μM in culture medium) models of ovarian damage in mice simulating clinical doses and found that IBU not only caused ovarian damage in mice in a dose-response relationship, but also decreased estradiol (E2) and prostaglandin E2 (PGE2) levels in serum/media with increasing IBU doses. In damaged ovaries, the cyclooxygenase 2 (COX2)-PGE2 pathway is inhibited, the Hippo pathway is activated, circPVT1 is decreased, and miR-149 is elevated. TT-10 is an activator of YES-associated protein (YAP)-transcriptional enhancer factor domain activity. Then, 100 μM IBU-induced ovarian damage model was selected for YAP activation (Hippo pathway inhibition) experiment, and TT-10 was found to interfere with IBU-induced ovarian damage and increase E2 level in the medium, and 10 μM of TT-10 had the best protective effect. TT-10 also inhibited the Hippo pathway, activated the COX2-PGE2 pathway, elevated circPVT1 expression, and decreased miR-149 expression in the ovary. It has been hypothesized that clinical doses of IBU damage mouse ovaries by inhibiting COX2-PGE2 and activating the Hippo pathway, whereas TT-10 protects the ovaries through the inverse regulation of these two pathways.

Prostaglandin E2 promotes Th17 differentiation induces corneal epithelial cell apoptosis and participates in the progression of dry eye

This study is mainly based on T helper type 17 (Th17) cells analysis of the mechanism of prostaglandin E2 (PGE2) promoting the progression of dry eye (DE). Scopolamine and dry environment were used to induce mice DE model. Celecoxib was used to inhibit PGE2. Corneal epithelial cells and CD4+ T cells were used to construct a co-culture system. The osmotic pressure was increased by adding NaCl to simulate DE in vitro. AH6809 and E7046 were used to pre-culture to inhibit EP2/4 in T cells to verify the effect of exogenous PGE2 on Th17 cell differentiation and corneal epithelial cell apoptosis. The function of Th17 cells was analyzed by detecting RORγt and interleukin-17 (IL-17). PGE2 was instilled on the ocular surface to induce DE symptoms of mice. AH6809 and E7046 were used to inhibit EP2/4. The corneal epithelial cell apoptosis was observed by TUNEL. The proportion of Th17 cells in corneal tissue and draining lymph nodes (DLNs) was detected by flow cytometry. In DE mice, the concentration of PGE2 and IL-17 increased in tears, and the proportion of Th17 increased, while inhibition of PGE2 alleviated the symptoms of DE and inhibited Th17 differentiation. Hypertonic environment induces corneal epithelial cells to secrete PGE2. PGE2 promoted the expression of EP2/4 and the differentiation of Th17 cells in vitro. The hypertonic environment promoted PGE2 level and the apoptosis of corneal epithelial cells in the co-culture system. PGE2 alone did not cause corneal epithelial cell apoptosis, while PGE2 promoted apoptosis by promoting Th17. Blocking EP2/4 reduced the induction of Th17 differentiation by PGE2 and the promoted corneal epithelial cell apoptosis. Animal experiments showed that exogenous PGE2 induced DE symptoms. Blocking EP2/4 not only inhibited the proportion of Th17, but also alleviated the apoptosis of corneal epithelial cells caused by PGE2. PGE2 induces aggravation of inflammation by promoting the level of Th17 in the ocular surface, and causes corneal epithelial cell apoptosis, thereby participating in the progression of DE.

In Vitro Assessment of Anti-Adipogenic and Anti-Inflammatory Properties of Black Cumin (Nigella sativa L.) Seeds Extract on 3T3-L1 Adipocytes and Raw264.7 Macrophages.

Background and Objectives: This study evaluated the in vitro anti-adipogenic and anti-inflammatory properties of black cumin (Nigella sativa L.) seed extract (BCS extract) as a potential candidate for developing herbal formulations targeting metabolic disorders. Materials and Methods: We evaluated the BCS extract by assessing its 2,2-diphenyl-1-picrohydrazyl (DPPH) radical scavenging activity, levels of prostaglandin E2 (PGE2) and nitric oxide (NO), and mRNA expression levels of key pro-inflammatory mediators. We also quantified the phosphorylation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPK) signaling molecules. To assess anti-adipogenic effects, we used differentiated 3T3-L1 cells and BCS extract in doses from 10 to 100 μg/mL. We also determined mRNA levels of key adipogenic genes, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/BEPα), adipocyte protein 2 (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), and sterol-regulated element-binding protein 1c (SREBP-1c) using real-time quantitative polymerase chain reaction (qPCR). Results: This study showed a concentration-dependent DPPH radical scavenging activity and no toxicity at concentrations up to 30 μg/mL in Raw264.7 cells. BCS extract showed an IC50 of 328.77 ± 20.52 μg/mL. Notably, pre-treatment with BCS extract (30 μg/mL) significantly enhanced cell viability in lipopolysaccharide (LPS)-treated Raw264.7 cells. BCS extract treatment effectively inhibited LPS-induced production of PGE2 and NO, as well as the expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), interleukin (IL)-1β and IL-6, possibly by limiting the phosphorylation of p38, p65, inhibitory κBα (I-κBα), and c-Jun N-terminal kinase (JNK). It also significantly attenuated lipid accumulation and key adipogenic genes in 3T3-L1 cells. Conclusions: This study highlights the in vitro anti-adipogenic and anti-inflammatory potential of BCS extract, underscoring its potential as a promising candidate for managing metabolic disorders.

Prostaglandin E2 Boosts the Hyaluronan-Mediated Increase in Inflammatory Response to Lipopolysaccharide by Enhancing Lyve1 Expression.

Macrophages are a highly versatile and heterogenic group of immune cells, known for their involvement in inflammatory reactions. However, our knowledge about distinct subpopulations of macrophages and their specific contribution to the resolution of inflammation remains incomplete. We have previously shown, in an in vivo peritonitis model, that inhibition of the synthesis of the pro-inflammatory lipid mediator prostaglandin E2 (PGE2) attenuates efficient resolution of inflammation. PGE2 levels during later stages of the inflammatory process further correlate with expression of the hyaluronan (HA) receptor Lyve1 in peritoneal macrophages. In the present study, we therefore aimed to understand if PGE2 might contribute to the regulation of Lyve1 and how this might impact inflammatory responses. In line with our in vivo findings, PGE2 synergized with dexamethasone to enhance Lyve1 expression in bone marrow-derived macrophages, while expression of the predominant hyaluronan receptor CD44 remained unaltered. PGE2-mediated Lyve1 upregulation was strictly dependent on PGE2 receptor EP2 signaling. While PGE2/dexamethasone-treated macrophages, despite their enhanced Lyve1 expression, did not show inflammatory responses upon stimulation with low (LMW) or high-molecular-weight hyaluronan (HMW)-HA, they were sensitized towards LMW-HA-dependent augmentation of lipopolysaccharide (LPS)-induced inflammatory responses. Thus, Lyve1-expressing macrophages emerged as a subpopulation of macrophages integrating inflammatory stimuli with extracellular matrix-derived signals.

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

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. 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. 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. 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.

The Effect of Three Ten-Day Courses of Yoga Exercises and Zinc Sulfate Supplementation on Prostaglandin E in Non-athletic Young Women with Primary Dysmenorrhea

Background: Dysmenorrhea (painful menstruation) is a common health problem in women of reproductive age, affecting the individual’s health, job performance, and quality of life. Objectives: This research investigated the effect of three ten-day yoga courses and zinc sulfate on primary dysmenorrhea in non-athlete girls. Methods: Forty-eight girls (18 to 25 years old) suffering from dysmenorrhea in Karaj participated in this clinical trial. Cluster sampling was used to select the subjects, and they were allocated to four groups: The placebo group, the yoga and placebo group, the zinc sulfate group, and the yoga and zinc sulfate group. Before the research, the serum levels of prostaglandin E were measured in the laboratory using the ELISA method. Then, the yoga training group (from the 22nd day of menstruation to the third day of bleeding for ten days, 45 minutes every day) performed yoga exercises. The exercise program of this research was five asanas. Also, yoga, stretching, strength training, and breathing and relaxation techniques were performed between the asanas training, which mainly involved the abdomen and lower back. Results: The results showed that yoga exercises and zinc sulfate supplementation significantly affected (decreased) the levels of prostaglandin E in non-athlete girls (F1,43 = 17.564, P = 0.001, η = 0.290). Also, exercise alone affected prostaglandin E levels significantly (P &lt; 0.05) compared to other groups. However, the supplement alone did not influence prostaglandin E levels significantly (P &gt; 0.05). In addition, exercises and zinc sulfate supplementation significantly affected anthropometric measures. Conclusions: According to the results, three ten-day yoga exercise programs and zinc sulfate supplements improved primary dysmenorrhea.