Prostaglandin E2 Production Research Articles

Selective mPGES-1 Inhibitor Ameliorated Adjuvant-Induced Arthritis in the Rat Model

Endogenous prostaglandin E2 (PGE2) plays an important role in maintaining the homeostasis conditions. However, the overexpression of PGE2 in response to various inflammatory stimulations is an important target of anti-inflammatory drugs. Both inducible COX-2 (cyclooxygenase-2) and mPGES-1 (microsomal prostaglandin E2 synthase-1) enzymes are responsible for the inflammatory overexpressed PGE2 production. Among them, mPGES-1 is regarded as a more promising ideal target for anti-inflammatory drugs without the gastrointestinal and cardiovascular side effects. As our continuous research for the discovery of novel mPGES-1 inhibitors, we have characterized MPO-0144 as a selective mPGES-1 inhibitor with a selectivity index of >270 over COX-1 and >25 over COX-2, respectively. Herein, we evaluated the anti-inflammatory effect of MPO-0144 in an adjuvant-induced arthritis rat model. MPO-0144 attenuated the inflammatory responses without severe gastrointestinal side effects and organ toxicities. These overall data suggest a possibility that MPO-0144 downregulates PGE2 production by potent mPGES-1 and weak COX-2 inhibitory activities, thus attenuating the paw swelling in AIA (adjuvant-induced arthritis) rat models. MPO-0144 also exhibited favorable ADMET profiles. However, MPO-0144 did not show any inhibitory effects on human mPGES-1 enzyme at a high concentration. Therefore, MPO-0144 represents a valuable pharmacological tool for the study of regulation of inducible mPGES-1 in an inflammatory arthritis rat model.

Prostaglandin E2 affects mitochondrial function in adult mouse cardiomyocytes and hearts

Prostaglandin E2 (PGE2) signals differently through 4 receptor subtypes (EP1-EP4) to elicit diverse physiologic/pathologic effects. We previously reported that PGE2 via its EP3 receptor reduces cardiac contractility and male mice with cardiomyocyte-specific deletion of the EP4 receptor (EP4 KO) develop dilated cardiomyopathy. The aim of this study was to identify pathways responsible for this phenotype. We performed ingenuity pathway analysis (IPA) and found that genes differentiating WT mice and EP4 KO mice were significantly overrepresented in mitochondrial (adj. p value = 6.28 × 10−26) and oxidative phosphorylation (adj. p value = 1.58 × 10−27) pathways. Electron microscopy from the EP4 KO hearts show substantial mitochondrial disarray and disordered cristae. Not surprisingly, isolated adult mouse cardiomyocytes (AVM) from these mice have reduced ATP levels compared to their WT littermates and reduced expression of key genes involved in the electron transport chain (ETC) in older mice. Moreover, treatment of AVM from C57Bl/6 mice with PGE2 or the EP3 agonist sulprostone resulted in changes of various genes involved in the ETC, measured by the Mitochondrial Energy Metabolism RT2-profiler assay. Lastly, the EP4 KO mice have reduced expression of superoxide dismuatse-2 (SOD2), whereas treatment of AVM with PGE2 or sulprostone increase superoxide production, suggesting increased oxidative stress levels in these EP4 KO mice. Altogether the current study supports the premise that PGE2 acting via its EP4 receptor is protective, while signaling through its other receptors, likely EP3, is deleterious.

Sexual dimorphism in melanocyte stem cell behavior reveals combinational therapeutic strategies for cutaneous repigmentation

Vitiligo is an autoimmune skin disease caused by cutaneous melanocyte loss. Although phototherapy and T cell suppression therapy have been widely used to induce epidermal re-pigmentation, full pigmentation recovery is rarely achieved due to our poor understanding of the cellular and molecular mechanisms governing this process. Here, we identify unique melanocyte stem cell (McSC) epidermal migration rates between male and female mice, which is due to sexually dimorphic cutaneous inflammatory responses generated by ultra-violet B exposure. Using genetically engineered mouse models, and unbiased bulk and single-cell mRNA sequencing approaches, we determine that manipulating the inflammatory response through cyclooxygenase and its downstream prostaglandin product regulates McSC proliferation and epidermal migration in response to UVB exposure. Furthermore, we demonstrate that a combinational therapy that manipulates both macrophages and T cells (or innate and adaptive immunity) significantly promotes epidermal melanocyte re-population. With these findings, we propose a novel therapeutic strategy for repigmentation in patients with depigmentation conditions such as vitiligo.

Neutrophil extracellular traps promote MASH fibrosis by metabolic reprogramming of HSC.

Metabolic dysfunction-associated steatohepatitis (MASH) fibrosis is a reversible stage of liver disease accompanied by inflammatory cell infiltration. Neutrophils extrude a meshwork of chromatin fibers to establish neutrophil extracellular traps (NETs), which play important roles in inflammatory response regulation. Our previous work demonstrated that NETs promote HCC in MASH. However, it is still unknown if NETs play a role in the molecular mechanisms of liver fibrosis. Following 12 weeks of Western diet/carbon tetrachloride, MASH fibrosis was identified in C57BL/6 mice with increased NET formation. However, NET depletion using DNase I treatment or mice knocked out for peptidyl arginine deaminase type IV significantly attenuated the development of MASH fibrosis. NETs were demonstrated to induce HSCs activation, proliferation, and migration through augmented mitochondrial and aerobic glycolysis to provide additional bioenergetic and biosynthetic supplies. Metabolomic analysis revealed markedly an altered metabolic profile upon NET stimulation of HSCs that were dependent on arachidonic acid metabolism. Mechanistically, NET stimulation of toll-like receptor 3 induced cyclooxygenase-2 activation and prostaglandin E2 production with subsequent HSC activation and liver fibrosis. Inhibiting cyclooxygenase-2 with celecoxib reduced fibrosis in our MASH model. Our findings implicate NETs playing a critical role in the development of MASH hepatic fibrosis by inducing metabolic reprogramming of HSCs through the toll-like receptor 3/cyclooxygenase-2/cyclooxygenase-2 pathway. Therefore, NET inhibition may represent an attractive treatment target for MASH liver fibrosis.

Effects of Curcuma longa (turmeric) and curcumin on the premenstrual syndrome and dysmenorrhea: A systematic review

Premenstrual syndrome (PMS) and dysmenorrhea, in addition to harming the physical and mental health of women, also disrupt their daily life and quality of life. We aimed to investigate the effects and underlying mechanisms of Curcuma longa (turmeric) and curcumin on PMS and dysmenorrhea. PRISMA guideline 2020 was followed for conducting this systematic review. Comprehensive literature searches were conducted across multiple databases, including PubMed, EMBASE, Web of Science, and Scopus. Finally, 17 articles were found after considering the study’s inclusion and exclusion criteria into account. Data were extracted and entered into an Excel file for further investigation and drew the results. Curcuma longa and curcumin affect PMS and dysmenorrhea through various mechanisms. They inhibit the activity of cyclooxygenase-2 (COX-2) and the production of prostaglandins, thus reducing inflammation and pain. Additionally, curcumin’s antioxidant properties protect against oxidative stress, and lipid peroxidation helps maintain hormonal balance, exert analgesic effects, and relieve the symptoms of PMS and dysmenorrhea. They also insert neurotransmitter modulatory properties, such as increased serotonin and dopamine levels, which may contribute to their antidepressant, and sedative effects. Curcuma longa and curcumin indicated promising therapeutic effects in reducing PMS and dysmenorrhea symptoms due to their anti-inflammatory and antioxidant effects. Although, further well-designed clinical trials are needed to establish their efficacy and optimal dosage.

Treponema pallidum protein Tp47 induced prostaglandin E2 to inhibit the phagocytosis in human macrophages.

During Treponema pallidum (T. pallidum) infection, the host's immune system actively engages in pursuit and elimination of T. pallidum, while T. pallidum skillfully employs various mechanisms to evade immune recognition. Macrophages exhibit incomplete clearance of T. pallidum invitro and the underlying mechanism of how T. pallidum resists the attack of macrophage remains unclear. To investigate the effect of T. pallidum membrane protein Tp47 on the phagocytosis of macrophages. THP-1-derived macrophages were used to investigate the role of Tp47 in the secretion of Prostaglandin E2 (PGE2) in macrophages and the mechanism by which Tp47 induced the production of PGE2, as well as the impact of PGE2 on the macrophage's phagocytosis. Tp47 (1-10 μg/mL) significantly inhibited the phagocytosis of latex beads and T. pallidum in macrophages (p ≤ 0.05). PGE2 production by macrophages could be induced by Tp47, and the phagocytic function of macrophages could be restored using PGE2 antibody. Tp47 produced PGE2 by activating the PERK/NF-κB/COX-2 pathway in macrophages. Inhibitors targeting PERK, NF-κB and COX-2, respectively, reduced the level of PGE2 and restored the phagocytic function of macrophages. Tp47-induced PGE2 production via the PERK/NF-κB/COX-2 pathway contributed to macrophage phagocytosis inhibition, which potentially contributes to immune evasion during the T. pallidum infection.

The IL-4/13-induced production of M2 chemokines by human lung macrophages is enhanced by adenosine and PGE2

Background and purposeLung macrophages (LMs) are critically involved in respiratory diseases. The primary objective of the present study was to determine whether or not an adenosine analog (NECA) and prostaglandin E2 (PGE2) affected the interleukin (IL)-4- and IL-13-induced release of M2a chemokines (CCL13, CCL17, CCL18, and CCL22) by human LMs. Experimental ApproachPrimary macrophages isolated from resected human lungs were incubated with NECA, PGE2, roflumilast, or vehicle and stimulated with IL-4 or IL-13 for 24 h. The levels of chemokines and PGE2 in the culture supernatants were measured using ELISAs and enzyme immunoassays. Key resultsExposure to IL-4 (10 ng/mL) and IL-13 (50 ng/mL) was associated with greater M2a chemokine production but not PGE2 production. PGE2 (10 ng/mL) and NECA (10-6 M) induced the production of M2a chemokines to a lesser extent but significantly enhanced the IL-4/IL-13-induced production of these chemokines. At either a clinically relevant concentration (10-9 M) or at a concentration (10-7 M) that fully inhibited phosphodiesterase 4 (PDE4) activity, roflumilast did not increase the production of M2a chemokines and did not modulate their IL-13-induced production, regardless of the presence or absence of PGE2. ConclusionsNECA and PGE2 enhanced the IL-4/IL-13-induced production of M2a chemokines. The inhibition of PDE4 by roflumilast did not alter the production of these chemokines. These results contrast totally with the previously reported inhibitory effects of NECA, PGE2, and PDE4 inhibitors on the lipopolysaccharide-induced release of tumor necrosis factor alpha and M1 chemokines in human LMs.

Development of in situ forming implants for controlled delivery of punicalagin

Due to efficient drainage of the joint, the development of intra-articular depots for long-lasting drug release is a difficult challenge. Moreover, a disease-modifying osteoarthritis drug (DMOAD) that can effectively manage osteoarthritis has yet to be identified. The current study was undertaken to explore the potential of injectable, in situ forming implants to create depots that support the sustained release of punicalagin, a promising DMOAD. In vitro experiments demonstrated punicalagin’s ability to suppress production of interleukin-1β and prostaglandin E2, confirming its chondroprotective properties. Regarding the entrapment of punicalagin, it was demonstrated by LC-MS/MS to be stable within PLGA in situ forming implants for several weeks and capable of inhibiting collagenase upon release. In vitro punicalagin release kinetics were tunable through variation of solvent, PLGA lactide:glycolide ratio, and polymer concentration, and an optimized formulation supported release for approximately 90 days. The injection force of this formulation steadily increased with plunger advancement and higher rates of advancement were associated with greater forces. Although the optimal formulation was highly cytotoxic to primary chondrocytes if cells were exposed immediately or shortly after implant formation, upwards of 70 % survival was achieved when the implants were first allowed to undergo a 24–72 h period of phase inversion prior to cell exposure. This study demonstrates a PLGA-based in situ forming implant for the controlled release of punicalagin. With modification to address cytotoxicity, such an implant may be suitable as an intra-articular therapy for OA.

Anti inflammatory and human chondrocyte protective effect of Drynariae rhizoma extract

Purpose: To evaluate the anti-inflammatory properties of Drynariae rhizome (Polypodiaceae) extract (DRE) on lipopolysaccharide RAW264.7 macrophage cells and its protective effects on interleukin (IL)-1β-stimulated SW1353 chondrocyte cells.
 Methods: The anti-inflammatory effect of DRE (12.5, 25, 50, and 100 µg/mL) were measured by 5-lipooxygenase (LO) and cyclooxygenase (COX)-2 enzyme inhibitory activities, nitric oxide (NO) production in LPS-stimulated RAW264.7 cells using Griess reagent assay. Prostaglandins (PGE2) and leukotriene (LTB4) production were measured using enzyme-linked immunosorbent assay (ELISA). To investigate the protective effect on chondrocytes, the level of matrix metalloproteinases (MMP)-3, -9, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 was determined using zymography assay and ELISA kit in SW1353 cells stimulated with IL-1β.
 Results: Drynariae rhizome (Polypodiaceae) extract (DRE) had a significant (p < 0.05) inhibitory effect on 5-LO and COX-2 enzymes in a concentration-dependent manner compared to untreated group. In RAW264.7 cells, levels of NO, PGE2 and LTB4 of DRE group were significantly (p < 0.05) decreased in study group (treated with DRE) at 12.5 μg/mL compared to the group treated with LPS (100 ng/mL) alone. Additionally, in SW1353 human chondrocytes stimulated with IL-1β, MMP-3 and MMP-9 were significantly (p < 0.05) suppressed in DRE-treated group compared to IL-1β group alone, with no significant impact on TIMP-1 production.
 Conclusion: Drynariae rhizome (Polypodiaceae) extract (DRE) possesses anti-inflammatory and cartilage protection effects. It therefore has the potential to be developed as an effective natural pharmaceutical agent for inflammation or osteoarthritis.

Cyclooxygenase-2/prostaglandin E2 pathway regulates infectious bronchitis virus replication in avian macrophages.

Infectious bronchitis virus (IBV) is a significant respiratory pathogen that affects chickens worldwide. As an avian coronavirus, IBV leads to productive infection in chicken macrophages. However, the effects of IBV infection in macrophages on cyclooxygenase-2 (COX-2) expression are still to be elucidated. Therefore, we investigated the role of IBV infection on the production of COX-2, an enzyme involved in the synthesis of prostaglandin E2 (PGE2) in chicken macrophages. The chicken macrophage cells were infected with two IBV strains, and the cells and culture supernatants were harvested at predetermined time points to measure intracellular and extracellular IBV infection. IBV infection was quantified as has been the COX-2 and PGE2 productions. We found that IBV infection enhances COX-2 production at both mRNA and protein levels in chicken macrophages. When a selective COX-2 antagonist was used to reduce the COX-2 expression in macrophages, we observed that IBV replication decreased. When IBV-infected macrophages were treated with PGE2 receptor (EP2 and EP4) inhibitors, IBV replication was reduced. Upon utilizing a selective COX-2 antagonist to diminish PGE2 expression in macrophages, a discernible decrease in IBV replication was observed. Treatment of IBV-infected macrophages with a PGE2 receptor (EP2) inhibitor resulted in a reduction in IBV replication, whereas the introduction of exogenous PGE2 heightened viral replication. Additionally, pretreatment with a Janus-kinase two antagonist attenuated the inhibitory effect of recombinant chicken interferon (IFN)-γ on viral replication. The evaluation of immune mediators, such as inducible nitric oxide (NO) synthase (iNOS), NO, and interleukin (IL)-6, revealed enhanced expression following IBV infection of macrophages. In response to the inhibition of COX-2 and PGE2 receptors, we observed a reduction in the expressions of iNOS and IL-6 in macrophages, correlating with reduced IBV infection. Overall, IBV infection increased COX-2 and PGE2 production in addition to iNOS, NO, and IL-6 expression in chicken macrophages in a time-dependent manner. Inhibition of the COX-2/PGE2 pathway may lead to increased macrophage defence mechanisms against IBV infection, resulting in a reduction in viral replication and iNOS and IL-6 expressions. Understanding the molecular mechanisms underlying these processes may shed light on potential antiviral targets for controlling IBV infection.

Low-Molecular-Weight Hydrolysate from Black Goat Extract Had Antioxidative and Anti-Inflammatory Effects in Macrophage Cells via Inhibition of MAPKs and NF-κB Pathways

This study evaluated the antioxidative and anti-inflammatory effects of a low-molecular-weight hydrolysate derived from black goat extract using alcalase, ProteAX, and trypsin (APT6 < 3 kDa). The APT6 < 3 kDa exhibited high antioxidative activities with estimated contents of 41.24% for antioxidative amino acids and 49.55% for hydrophobic amino acids. APT6 < 3 kDa inhibited nitric oxide and prostaglandin E2 production in RAW 264.7 cells induced by lipopolysaccharide (p<0.05), which was accompanied by the inhibition of inducible nitric oxide synthase and cyclooxygenase-2 protein expression. Additionally, APT6 < 3 kDa downregulated the mRNA expression and production of TNF-α and IL-1β (p<0.05). Mechanistically, these anti-inflammatory effects of APT6 < 3 kDa were shown by downregulating the MAPK and NF-κB pathways in a dose-dependent manner. Overall, 43 peptides were isolated from a certain fraction (F5) of APT6 < 3 kDa, demonstrating high antioxidative and anti-inflammatory activities. These results suggest that identified peptides from APT6 < 3 kDa possess natural antioxidants and hold potential as anti-inflammatory agents.

Silica Nanoparticles Shed Light on Intriguing Cellular Pathways in Human Tracheal Smooth Muscle Cells: Revealing COX-2/PGE2 Production through the EGFR/Pyk2 Signaling Axis.

The use of manufactured silica nanoparticles (SiNPs) has become widespread in everyday life, household products, and various industrial applications. While the harmful effects of crystalline silica on the lungs, known as silicosis or chronic pulmonary diseases, are well understood, the impact of SiNPs on the airway is not fully explored. This study aimed to investigate the potential effects of SiNPs on human tracheal smooth muscle cells (HTSMCs). Our findings revealed that SiNPs induced the expression of cyclooxygenase-2 (COX-2) mRNA/protein and the production of prostaglandin E2 (PGE2) without causing cytotoxicity. This induction was transcription-dependent, as confirmed by cell viability assays and COX-2 luciferase reporter assays. Further analysis, including Western blot with pharmacological inhibitors and siRNA interference, showed the involvement of receptor tyrosine kinase (RTK) EGF receptor (EGFR), non-RTK Pyk2, protein kinase Cα (PKCα), and p42/p44 MAPK in the induction process. Notably, EGFR activation initiated cellular signaling that led to NF-κB p65 phosphorylation and translocation into the cell nucleus, where it bound and stimulated COX-2 gene transcription. The resulting COX-2 protein triggered PGE2 production and secretion into the extracellular space. Our study demonstrated that SiNPs mediate COX-2 up-regulation and PGE2 secretion in HTSMCs through the sequential activation of the EGFR/Pyk2/PKCα/p42/p44MAPKs-dependent NF-κB signaling pathway. Since PGE2 can have both physiological bronchodilatory and anti-inflammatory effects, as well as pathological pro-inflammatory effects, the increased PGE2 production in the airway might act as a protective compensatory mechanism and/or a contributing factor during airway exposure to SiNPs.

Chalcone derivatives' interaction with human serum albumin and cyclooxygenase-2.

Chalcone derivatives are an extremely valuable class of compounds, primarily due to the keto-ethylenic group, CO-CH[double bond, length as m-dash]CH-, they contain. Moreover, the presence of a reactive α,β-unsaturated carbonyl group confers upon them a broad range of pharmacological properties. Recent developments in heterocyclic chemistry have led to the synthesis of chalcone derivatives, which have been biologically investigated for their activity against certain diseases. In this study, we investigated the binding of new chalcone derivatives with COX-2 (cyclooxygenase-2) and HSA (Human Serum Albumin) using spectroscopic and molecular modeling studies. COX-2 is commonly found in cancer and plays a role in the production of prostaglandin E (2), which can help tumors grow by binding to receptors. HSA is the most abundant protein in blood plasma, and it transports various compounds, including hormones and fatty acids. The conformation of chalcone derivatives in the HSA complex system was established through fluorescence steady and excited state spectroscopy techniques and FTIR analyses. To gain a more comprehensive understanding, molecular docking, and dynamics were conducted on the target protein (COX-2) and transport protein (HSA). In addition, we conducted density-functional theory (DFT) and single-point DFT to understand intermolecular interaction in protein active sites.

Menstrual Problems: Menorrhagia and Primary Dysmenorrhagia

Menstrual problems can considerably affect a girl’s status in life, accompanied by two universal issues: menorrhagia and basic dysmenorrhea. Menorrhagia, characterized by difficult menstrual draining, is a condition in which a woman experiences extended periods or excessive blood flow. This condition may incapacitate you, leading to blood deficiency, fatigue, and public restraints. The underlying causes of menorrhagia can change, including hormonal imbalances, uterine Fibroids, or added medical environments, which typically include a particularized record of what happened and a physical examination attended by potential situations such as cure, hormonal therapy, or surgical attack. Primary dysmenorrhea, in another way, refers to harsh menstrual cramps without some fundamental healing condition. It is a common issue among daughters and usually occurs during the first few days of the period. The exact cause of basic dysmenorrhea is not well understood; however, it is expected to be associated with prostaglandin production and uterine shortening. Women with primary dysmenorrhea grant permission for sharp, incapacitating pain, nausea, and additional discomfort, which upset their regular lives. Management options include pain relievers, hormonal contraceptives, behavioral changes, and heat therapy.

Aspirin in a new role in human body

In 1897, German chemist Felix Hoffman synthesized acetylsalicylic acid, known as aspirin, which revolutionized its widespread modern use for pain relief. Aspirin acts as an inhibitor of cyclooxygenase-1 (COX-1) and has a modifying effect on the enzymatic activity of cyclooxygenase-2 (COX-2). It inhibits the production of prostaglandins, crucial for various physiological processes, and has been linked to a reduced risk of pre-eclampsia and preterm delivery before 34 weeks of pregnancy. However, aspirin's COX-1 inhibition is irreversible and long-lasting, requiring new enzymes to replace those acetylated. Low-dose aspirin has been reported to increase bone mineral density (BMD) in elderly individuals, coinciding with the growing prevalence of osteoporosis. However, a definitive connection between the use of low-dose aspirin and BMD remains elusive. A study examined the relationship between low-dose aspirin use and BMD in adults aged 50 to 80. A higher BMD in the femur, intertrochanter, and L1 regions compared to those who do not use aspirin was reported. However, the abstract acknowledges limitations and emphasizes the need for future research, including randomized controlled trials, to establish a causal relationship between low-dose aspirin use and enhanced bone density.

Cold Exposures in Relation to Dysmenorrhea among Asian and White Women.

Dysmenorrhea is highly prevalent, ranging from 16% to 91% among women, and it can lead to multiple reproductive disorders. However, risk factors associated with dysmenorrhea remain unexamined. Cold exposures can significantly disturb blood circulation and prostaglandin production in the uterus, leading to dysmenorrhea. This study investigated the relationship between cold exposures and dysmenorrhea, as well as potential disparities between Asians and Whites and the potential cultural influences on these associations. This was a cross-sectional survey among 197 Asian and 222 non-Asian women recruited from the U.S., with more than 40% from California. We assessed cold exposures, such as the frequency of consumption of cold water/drinks and ice cream, as well as room temperatures at home and public places, for both summer and winter over the past 12 months. The type of cold exposure associated with dysmenorrhea differs between Asian and White women. We found that among Asian women, a higher frequency of ice cream consumption in winter (beta = 1.19, p = 0.0002 when comparing high to low categories) was associated with dysmenorrhea; however, among White women, increased consumption of cold water/drinks in winter (beta = 0.49, p = 0.04 when comparing high to low categories) was also associated with dysmenorrhea. Higher home room temperatures in winter were associated with reduced severity of dysmenorrhea among White women but not among Asian women. All these associations supported our hypothesis and were stronger among women who lived in states with colder winters. However, there are a few exceptions. For instance, women who drank cold water/drinks less frequently during their menstrual period were more likely to experience more severe dysmenorrhea. In conclusion, this study provides crucial evidence to support the link between cold exposures and dysmenorrhea among Asians and Whites. The associations contradictory to our hypothesis are likely due to reserved causation influenced by Asian cultural practice. This paper sheds light on an understudied area that profoundly affects women's quality of life.

Naproxen administration affects murine late folliculogenesis, reduces granulosa cell proliferation and the number of ovulated oocytes

Naproxen reduces the production of prostaglandins via inhibition of the cyclooxygenase. Studies have shown that its administration in women can be related to failed ovulation. Therefore, preclinical investigations must be performed in order to investigate its effects in experimental models. Thus, the aim of this study was to evaluate the effects of naproxen on murine folliculogenesis, ovulation, and female fertility. Female C57BL/6 mice (n = 128 - 6 weeks old) were divided into Control, low (10 mg/kg), and high naproxen (50 mg/kg) groups, who were treated for 8 days and directed to morphofunctional analyses. Follicular quantification showed a reduced percentage of antral follicles in naproxen-treated animals. These treated animals also showed smaller oocytes included in secondary and antral follicles, and the diameter of secondary and antral follicles was also reduced. A reduction in the percentage of Ki67-positive granulosa cells was observed in treated animals that also showed down-regulation of Igf1r compared to control. After an ovarian stimulation protocol, naproxen-treated animals showed a reduction in the percentage of secondary and antral follicles, a reduced number of ovulated oocytes and, corpora lutea, and an increased number of failed ovulations. Finally, naproxen-treated animals also showed a reduction in mating index and pregnancy rate. Our findings suggested that, in mice, naproxen administration (eight days treatment) negatively affects molecular and morphological aspects related to late folliculogenesis, ovulation, and fertility.

Application of Aspirin for Rheumatoid Arthritis and Myocardial Infarction Treatment

With the intensification of the aging process of the population, the disease problems of the elderly are particularly prominent. Rheumatoid arthritis and myocardial infarction are common diseases in the elderly. The main component of aspirin has been used to treat fever since 1763, and then the role of aspirin was discovered by humans. In modern daily life, aspirin is used for anti-inflammation, pain relief, and inhibition of thrombus formation. The subject of this research is how recent experiments demonstrate the effectiveness of aspirin for these two diseases. Research done by different teams has shown that aspirin inhibits a catalyst called COX that catalyzes the production of prostaglandins for rheumatoid arthritis treatment, leading to the relief of skeletal muscle pain and inflammation. In the treatment of myocardial infarction, aspirin prevents the accumulation of platelets to reduce the formation of thrombosis. Among the drug that can treat these two diseases, aspirin can be said to be the most effective drug with the least side effects.

Передчасно закрита артеріальна протока: можливі ризики для новонародженого

Premature closure of the fetal ductus arteriosus is a rare phenomenon that results in increased right ventricular pressure, leading to the development of isolated right ventricular hypertrophy, high pulmonary hypertension, and even death. Purpose - to present a rare clinical case of prenatally closed ductus arteriosus in a newborn boy, that clinically manifested by severe respiratory failure immediately after birth. Clinical case. The child was admitted to the neonatal intensive care unit 5 hours after delivery with clinical signs of severe respiratory failure, child was oxygen-dependent. It is known from the anamnesis that the child was delivered by urgent cesarean section on the basis of a prenatally diagnosed prematurely closed arterial duct. A week before the delivery, the mother had an acute respiratory viral infection accompanied by high fever, which was treated with high doses of over-the-counter ibuprofen. The 2D echocardiography showed severe hypertrophy of the right ventricular wall and tricuspid insufficiency, which was caused by premature closure of the ductus arteriosus. The flow through the ductus arteriosus was not determined. Aortic coarctation as a possible cause of right ventricular hypertrophy in the newborn period was excluded. The infant was switched to constant positive pressure artificial ventilation (CPAP) to reduce pulmonary vascular resistance and afterload of the right ventricle. Over the next 3-4 weeks of oxygen therapy, the child's general condition improved significantly. Hypertrophy of the right ventricular wall regressed to normal size, the child grows and develops according to age. Conclusions. Premature prenatal closure of the arterial duct can be idiopathic or caused drugs intake that suppress prostaglandin production late in the pregnancy. Pregnant women should be counseled about the potential side effects on the fetus caused by the use of NSAIDs, especially in the third trimester of pregnancy. Urgent delivery and oxygen therapy contribute to the regression of intracardiac changes and significantly improve general condition of the child. The study was conducted in accordance with the principles of the Declaration of Helsinki. The informed consent of the child’s parents was obtained for the study. No conflict of interests was declared by the authors.

ANALGESIC POWER OF THE INSOLUBLE FRACTION N-HEXANE OF MELINJO LEAVES (Gnetum gnemon L.) IN SWISS MICE (Mus musculus)

Melinjo (Gnetum gnemon L.) contains various secondary metabolites, including alkaloids, flavonoids, saponins, and tannins. Flavonoids function as analgesics and inhibit cyclooxygenase enzymes, which reduce prostaglandin production and pain. This study aimed to determine the analgesic power of the n-hexane-insoluble fraction of melinjo leaves (Gnetum gnemon L.) as an effective analgesic in male white mice (Mus musculus) and to determine the most effective analgesic dose. This research was conducted using test animals of 25 male white mice (Mus musculus) divided into 5 groups, each consisting of 5 mice. The negative control group (Na-CMC) was 0.5%, the positive control group received a mefenamic acid dose of 65 kg/BW, and the insoluble fraction hexane group (ifh) received doses of 50 mg/kg BW, 100 mg/kg BW, and 200 mg/kg BW. The chemical stimulus was administered at a dose of 400 mg/kg body weight acetic acid. The number of wriggles in male white mice (Mus musculus) was measured every 10 minutes for 60 minutes. The results of the study showed a significant difference between the negative control (Na-CMC 0.5%) and various doses of insoluble fraction hexane groups, while the positive control (mefenamic acid 65 mg/kg BB) showed no difference with ifh doses of 100 mg/kg BB and 200 mg/kg BB ...