20,520 results on '"PROSTAGLANDIN E2"'
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2. Prostaglandin E2 accumulation is closely associated with S. aureus-infected bovine endometritis
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Liu, Kun, Pei, Le, Shen, Yuan, Wu, Jindi, Qian, Yinghong, Zhang, Nan, Mao, Wei, and Cao, Jinshan
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- 2024
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3. Uteroovarian pathway for embryo-empowered maintenance of the corpus luteum in farm animals
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Ginther, O.J.
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- 2024
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4. Pyrogenic and inflammatory mediators are produced by polarized M1 and M2 macrophages activated with D-dimer and SARS-CoV-2 spike immune complexes
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Park, Yun-Jong, Acosta, David, Rubel Hoq, Mohammad, Khurana, Surender, Golding, Hana, and Zaitseva, Marina
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- 2024
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5. Prostaglandin E2 promotes Th17 differentiation induces corneal epithelial cell apoptosis and participates in the progression of dry eye
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Zhang, Weijia, Yin, Jianwei, Deng, Yachun, Gong, Yu, Sun, Xiaoyu, and Chen, Jingyao
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- 2024
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6. Prostaglandin E2 and myocarditis; friend or foe?
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Bryson, Timothy D. and Harding, Pamela
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- 2023
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7. Prostaglandin pathways in equine myometrium regulations: endometrosis progression.
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Piotrowska-Tomala, Katarzyna K., Szóstek-Mioduchowska, Anna Z., Drzewiecka, Ewa M., Jonczyk, Agnieszka W., Wójtowicz, Anna, Wrobel, Michał H., Ferreira-Dias, Graca, and Skarzynski, Dariusz J.
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UTERINE contraction ,GENETIC transcription ,ESTRUS ,MARES ,MYOMETRIUM - Abstract
Introduction: Prostaglandins (PG) are important regulators of the myometrial contractility in mammals. Endometrosis, a condition characterized by morphological changes in the equine endometrium, also affects endometrial secretory function. However, it remains unclear whether and how endometrosis affects myometrial function. Methods: This study investigated: (i) mRNA transcription of genes encoding specific enzymes responsible for PG synthesis, such as prostaglandin—endoperoxide synthase (PTGS2), PGE
2 synthase (PTGES), PGF2α synthase (PTGFS) and PG receptors : PGE2 receptors (PTGER1- 4), and PGF2α receptor (PTGFS) in equine myometrium and, (ii) the effects of PGE2 and PGF2α on myometrial contractile activity, during endometrosis in mares. The myometria used in experiments 1 and 2 were collected from mares in the mid-luteal (n = 23) and follicular (n = 20) phases of the estrous cycle, according to the histological classification of the endometrium (Kenney and Doig categories I, IIA, IIB, and III). Results: In experiment 1, changes in mRNA transcription of PG synthase or PG receptors in the myometrium during the course of endometrosis were determined using qPCR. During the mid-luteal phase, myometrial mRNA transcription of PTGES increased in mares with endometrial category IIB compared to category I. However, myometrial mRNA transcription of PTGER1 decreased during the progression of endometrosis compared to category I. During the follicular phase, mRNA transcription of PTGER1 and PTGER2 increased in mares with endometrial categories III or IIA, respectively. In addition, mRNA transcription of PTGFS increased in mares with endometrium category IIA compared to category I. In experiment 2, the force of myometrial contractions was measured using an isometric concentration transducer. In the follicular phase, PGE2 decreased the force of contractions in mares with endometrial categories IIA, IIB, and III compared to the respective control groups. Prostaglandin F2α increased the force of myometrial contractions in mares with category IIA endometrium, whereas it decreased in category IIB compared to the respective control groups. Discussion: We concluded that in the progression of endometrosis there are changes in the myometrial transcription of mRNA encoding PG synthases and receptors , particularly PTGER1 and PTGER2. Mares with endometrosis had abnormal myometrial contractile responses to PG. These findings suggest that myometrial function may be compromised during the progression of endometrosis. [ABSTRACT FROM AUTHOR] more...- Published
- 2024
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8. Low Prostaglandin E 2 but High Prostaglandin D 2 , a Paradoxical Dissociation in Arachidonic Acid Metabolism in Aspirin-Exacerbated Airway Disease: Role of Airway Epithelium.
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Picado, César, Machado-Carvalho, Liliana, and Roca-Ferrer, Jordi
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EPITHELIAL cells , *INNATE lymphoid cells , *MAST cells , *CYCLOOXYGENASE 2 , *ARACHIDONIC acid - Abstract
In patients with aspirin-exacerbated respiratory disease (AERD), there is disparate regulation of prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2). Both prostanoids are synthesised by cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). However, while the basal synthesis of PGE2 tends to decrease, that of PGD2 increases in patients with AERD. Furthermore, both behave differently in response to the inhibitory action of NSAIDs on COX-1: PGE2 levels decrease while PGD2 increases. Increased PGD2 release correlates with nasal, bronchial, and extra-pulmonary symptoms caused by aspirin in AERD. The proposed hypothesis establishes that the answer to this paradoxical dissociation can be found in the airway epithelium. This is based on the observation that reduced COX-2 mRNA and/or protein expression is associated with reduced PGE2 synthesis in cultured fibroblast and epithelial cells from AERD compared to patients with asthma who are aspirin-tolerant and healthy subjects. The low production of PGE2 by the airway epithelium in AERD results in an excessive release of alarmins (TSLP, IL-33), which in turn contributes to activating group 2 innate lymphoid cells (ILC2s) and PGD2 synthesis by mast cells and eosinophils. Aspirin, by further increasing the diminished PGE2 regulation capacity in AERD, leads to respiratory reactions associated with the surge in PGD2 from mast cells and eosinophils. In summary, the downregulation of COX-2 and the subsequent low production of PGE2 by airway cells account for the apparently paradoxical increased production of PGD2 by mast cells and eosinophils at the baseline and after aspirin provocation in patients with AERD. A better understanding of the role of the airway epithelium would contribute to elucidating the mechanism of AERD. [ABSTRACT FROM AUTHOR] more...
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- 2024
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9. NitraTh epitope-based neoantigen vaccines for effective tumor immunotherapy.
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Zhang, Wanli, Shi, Xupeiyao, Huang, Shitong, Yu, Qiumin, Wu, Zijie, Xie, Wenbin, Li, Binghua, Xu, Yanchao, Gao, Zheng, Li, Guozhi, Qian, Qianqian, He, Tiandi, Zheng, Jiaxue, Zhang, Tingran, Tong, Yue, Deng, Danni, Gao, Xiangdong, Tian, Hong, and Yao, Wenbing more...
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T helper cells , *CANCER vaccines , *VACCINE effectiveness , *T cells , *IMMUNE response - Abstract
Neoantigen vaccines represent an emerging and promising strategy in the field of tumor immunotherapy. Despite their potential, designing an effective neoantigen vaccine remains a challenge due to the current limitations in predicting CD4+ T cell epitopes with high accuracy. Here, we introduce a novel approach to neoantigen vaccine design that does not rely on computational prediction of CD4+ T cell epitopes. Utilizing nitrated helper T cell epitope containing p-nitrophenylalanine, termed "NitraTh epitope," we have successfully engineered a series of tumor neoantigen vaccines capable of eliciting robust neoantigen-specific immune responses. With the help of NitraTh epitope, even mutations with low predicted affinity for MHC class I molecules were successfully induced to elicit neoantigen-specific responses. In H22 cell allograft and patient-derived xenograft (PDX) liver cancer mouse models, the NitraTh epitope-based neoantigen vaccines significantly suppressed tumor progression. More strikingly, through single-cell sequencing we found that the NitraTh epitope-based neoantigen vaccines regulate macrophage reprogramming and modulate macrophages to decrease the levels of the immunosuppressive molecule prostaglandin E2 (PGE2), which in turn reshapes the tumor immunosuppressive microenvironment. In summary, NitraTh epitope-based neoantigen vaccines possess the dual effects of potently activating neoantigen-specific immunity and alleviating immunosuppression, potentially providing a new paradigm for the design of tumor neoantigen vaccines. [ABSTRACT FROM AUTHOR] more...
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- 2024
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10. Clinical observation of Tuina plus electroacupuncture for migraine due to liver-Yang hyperactivity.
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Ke, Meijia, Hu, Yanping, and He, Shenghua
- Abstract
Copyright of Journal of Acupuncture & Tuina Science is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...
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- 2024
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11. Bondarzewia dickinsii Against Colitis-Associated Cancer Through the Suppression of the PI3K/AKT/COX-2 Pathway and Inhibition of PGE2 Production in Mice.
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Chen, Junliang, Liu, Shuai, Zhang, Xin, Dai, Xiaojing, Li, Yu, Han, Yonglin, and Li, Lanzhou
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Background: Bondarzewia dickinsii (BD) is a newly discovered edible mushroom with rich nutritional components. This study presents a thorough analysis of the components of BD, examining its inhibitory effects and the underlying mechanisms by which BD influences colitis-associated cancer (CAC). Methods: AOM/DSS-induced CAC mice (male C57BL/6) were used, and a histopathological analysis, intestinal microbiota assessment, and metabolomics profiling were carried out, as well as an evaluation of relevant proteins and factors, to investigate the CAC-inhibitory effects of BD. Results: BD is rich in nutritional components, including a total sugar content of 37.29% and total protein content of 24.9%. BD significantly diminished colon inflammation, as well as the size and quantity of tumors. In addition, BD modified the diversity of intestinal microbiota and changed the levels of 19 serum metabolites, including arachidonic acid. BD significantly reduced prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) in colon tissue. Furthermore, it was found to inhibit the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/COX-2 signaling pathway. Conclusions: In general, BD inhibited the onset and progression of CAC by modulating the composition of intestinal microbiota and metabolite levels, suppressing the PI3K/AKT/COX-2 pathway, and decreasing PGE2 expression. This study provides a significant reference for the development of BD as a dietary supplement and pharmaceutical agent in the treatment of CAC. [ABSTRACT FROM AUTHOR] more...
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- 2024
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12. Gardenia jasminoides fruit extract alleviates non-steroidal anti-inflammatory drug–induced gastropathy in rats.
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Worapongpaiboon, Rinrada, Kaikaew, Kasiphak, Werawatganone, Pornpen, Somanawat, Kanjana, Lerttanatum, Nathawadee, Klaikeaw, Naruemon, and Werawatganon, Duangporn
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FRUIT ,NONSTEROIDAL anti-inflammatory agents ,NF-kappa B ,DATA analysis ,RESEARCH funding ,NEUTROPHILS ,KRUSKAL-Wallis Test ,GLYCOPROTEINS ,CYTOCHEMISTRY ,DESCRIPTIVE statistics ,PLANT extracts ,RATS ,IMMUNOHISTOCHEMISTRY ,GENE expression ,MEDICINAL plants ,GASTRIC diseases ,ANIMAL experimentation ,WESTERN immunoblotting ,ONE-way analysis of variance ,STATISTICS ,NITRIC-oxide synthases ,STAINS & staining (Microscopy) ,DATA analysis software ,DINOPROSTONE - Abstract
Background: NSAID-induced gastropathy is a health burden that requires effective intervention. Among various prevention options, Gardenia jasminoides fruit extract (GJE) has demonstrated gastroprotective effects through anti-inflammatory pathways with a wide safety margin. However, the detailed molecular mechanisms of GJE regarding mucoprotective and anti-inflammatory effects remained to be explored. Therefore, we investigated the effects of GJE on NSAID-induced gastric injury in rats, focusing on the expression of the protective factors: prostaglandin E
2 (PGE2 ) and mucin 5AC (MUC5AC), and the aggravating factors: inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB). Methods: Twenty-four male Sprague–Dawley rats were assigned to three experimental groups (n = 8/group): the control group, the NSAIDs group receiving indomethacin to induce gastric ulcers, and the NSAIDs with GJE pretreatment (NSAIDs + GJE) group. After a two-day experimental period, the stomachs were collected for histopathological examination, immunohistochemical staining, and protein expression analysis in gastric tissue lysates. Results: The NSAIDs group exhibited severe neutrophil infiltration with ulcers upon gastric histopathological examination. Pretreatment with GJE attenuated NSAID-induced gastropathy, as evidenced by reduced neutrophil infiltration and decreased ulceration. Immunohistochemical staining and Western blotting demonstrated reduced expressions of PGE2 and MUC5AC, while the expressions of iNOS and NF-κB were increased following NSAID administration. In comparison to the NSAIDs group, the NSAIDs + GJE group exhibited higher expressions of PGE2 and MUC5AC and lower expressions of iNOS and NF-κB, providing evidence of the gastroprotective effects of GJE. Conclusions: Pretreatment with GJE alleviated NSAID-induced gastric ulcers by increasing the expression of PGE2 and MUC5AC and decreasing the expression of iNOS and NF-κB. This study contributes to the understanding of the mechanisms by which GJE attenuates NSAID-induced gastropathy. Further studies are required to validate the effect of GJE in clinical settings. [ABSTRACT FROM AUTHOR] more...- Published
- 2024
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13. Microsomal Prostaglandin E Synthase-1 Controls Colonic Prostaglandin E 2 Production and Exerts a Protective Effect on Colitis Induced by Trinitrobenzene Sulfonic Acid in Mice.
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Kojima, Fumiaki, Hioki, Yuka, Sekiya, Hiroki, Kashiwagi, Hitoshi, Iizuka, Yoshiko, Eto, Kei, Maehana, Shotaro, Kawakami, Fumitaka, Kubo, Makoto, Ishibashi, Hitoshi, and Ichikawa, Takafumi
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INFLAMMATORY bowel diseases , *CYCLOOXYGENASES , *TUMOR necrosis factors , *TH1 cells , *TRINITROBENZENE - Abstract
Microsomal prostaglandin E synthase-1 (mPGES-1) is an isozyme of the prostaglandin (PG) E synthase that acts downstream of cyclooxygenase and catalyzes the conversion of PGH2 to PGE2. The impact of genetic deletion of mPGES-1 on the development of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, a well-established model of inflammatory bowel disease (IBD), was investigated in this study. After administration of TNBS, mice deficient in mPGES-1 (mPGES-1−/− mice) showed more severe colitis than did wild-type (WT) mice. Histological examination revealed that mPGES-1−/− mice had markedly exacerbated symptoms of colitis. mPGES-1 expression was detectable in the colons of WT mice at both the mRNA and protein levels. Lack of mPGES-1 resulted in marked reduction of colonic PGE2 production. Our study also showed a significant increase in colonic expression of interleukin-17A (IL-17A), as well as interferon γ (IFNγ) and tumor necrosis factor α, during colitis in mPGES-1−/− mice compared with that in WT mice. Furthermore, loss of mPGES-1 increased the populations of IL-17A-producing T-helper (Th) 17 and IFNγ-producing Th1 cells in mesenteric lymph nodes. These results suggest that mPGES-1 is the main enzyme responsible for colonic PGE2 production and deficiency of mPGES-1 facilitates the development of colitis and T-cell-mediated immunity. mPGES-1 might, therefore, impact T-cell-related immune response associated with IBD. [ABSTRACT FROM AUTHOR] more...
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- 2024
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14. Distinct etiology of chronic inflammation – implications on degenerative diseases and cancer therapy.
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Maddipati, Krishna Rao
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ETIOLOGY of cancer ,ETIOLOGY of diseases ,DEGENERATION (Pathology) ,INFLAMMATORY mediators ,ANTI-inflammatory agents - Abstract
Acute inflammation is elicited by lipid and protein mediators in defense of the host following sterile or pathogen-driven injury. A common refrain is that chronic inflammation is a result of incomplete resolution of acute inflammation and behind the etiology of all chronic diseases, including cancer. However, mediators that participate in inflammation are also essential in homeostasis and developmental biology but without eliciting the clinical symptoms of inflammation. This non-inflammatory physiological activity of the so called 'inflammatory' mediators, apparently under the functional balance with anti-inflammatory mediators, is defined as unalamation (un-ala-mation). Inflammation in the absence of injury is a result of perturbance in unalamation due to a decrease in the anti-inflammatory mediators rather than an increase in the inflammatory mediators and leads to chronic inflammation. This concept on the etiology of chronic inflammation suggests that treatment of chronic diseases is better achieved by stimulating the endogenous anti-inflammatory mediators instead of inhibiting the 'inflammatory' mediator biosynthesis with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Furthermore, both 'inflammatory' and anti-inflammatory mediators are present at higher concentrations in the tumor microenvironment compared to normal tissue environments. Since cancer is a proliferative disorder rather than a degenerative disease, it is proposed that heightened unalamation , rather than chronic inflammation, drives tumor growth. This understanding helps explain the inefficacy of NSAIDs as anticancer agents. Finally, inhibition of anti-inflammatory mediator biosynthesis in tumor tissues could imbalance unalamation toward local acute inflammation triggering an immune response to restore homeostasis and away from tumor growth. [ABSTRACT FROM AUTHOR] more...
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- 2024
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15. Homocysteine aggravates intestinal inflammation through promotion of 5-LOX and COX-2 in IBD.
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Wang, Jing, Li, Lin, Chen, Pingbo, He, Chiyi, Niu, Xiaoping, and Mei, Qiao
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INFLAMMATORY bowel diseases ,CROHN'S disease ,REVERSE transcriptase polymerase chain reaction ,NF-kappa B ,ULCERATIVE colitis - Abstract
Background: Homocysteine (Hcy) is a pro-inflammatory molecule that has the potential to induce oxidative damage to cells and stimulate the release of inflammatory mediators. Hcy has been observed to enhance the production of inflammatory agents in vascular endothelial cells. However, the impact of Hcy on intestinal mucosal inflammation remains largely unexplored. Therefore, the objective of this study was to examine the potential of Hcy to stimulate the synthesis of inflammatory mediators and elucidate the underlying mechanisms in the intestinal mucosa. Methods: A total of 99 patients diagnosed with inflammatory bowel disease (IBD) and 10 healthy individuals were included in this study to assess the impact of homocysteine (Hcy) on the levels of leukotriene E4 (LTE4) and prostaglandin E2 (PGE2). The underlying mechanism responsible for the generation of LTE4 and PGE2 induced by Hcy was investigated using colitis rats and Caco-2 cells. 32 Sprague–Dawley rats were categorized into four groups: normal control, TNBS model, normal with Hcy injection, and TNBS model with Hcy injection. The mRNA expressions of 5-LOX, COX-2, and NF-κB were assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Caco-2 cells were subjected to treatment with varying concentrations (10, 20, 50, 100 μmol/L) of Hcy and incubated for different durations (1, 3, 6 h). The alterations in NF-κB activity, as well as the levels of Hcy, LTE4, and PGE2, were measured using enzyme-linked immunosorbent assay (ELISA). Results: The excretion of Hcy, LTE4, and PGE2 in urine exhibited significant increases in patients with inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC). In addition, Hcy demonstrated a significant increase in the expression of 5-LOX, COX-2, and NF-κB, as well as elevated levels of LTE4 and PGE2 in rats with colitis. Furthermore, Hcy was found to induce NF-κB activation and nuclear translocation, thereby contributing to the enhanced synthesis of LTE4 and PGE2 in Caco-2 cells. Conclusions: Hcy was found to enhance the expression of 5-LOX and COX-2 by activating NF-κB, thereby augmenting the production of LTE4 and PGE2, which ultimately exacerbates colonic inflammation in individuals with inflammatory bowel disease (IBD). [ABSTRACT FROM AUTHOR] more...
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- 2024
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16. The impact of trauma relevant concentrations of prostaglandin E2 on the anti-microbial activity of the innate immune system.
- Author
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Nicholson, Thomas, Belli, Antonio, Lord, Janet M., and Hazeldine, Jon
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MONONUCLEAR leukocytes ,NATURAL immunity ,PROTEIN kinase inhibitors ,THERAPEUTICS ,PHAGOCYTOSIS - Abstract
Background: The mechanisms underlying the state of systemic immune suppression that develops following major trauma are poorly understood. A post-injury increase in circulating levels of prostaglandin E
2 (PGE2 ) has been proposed as a contributory factor, yet few studies have addressed how trauma influences PGE2 biology. Methods: Blood samples from 95 traumatically-injured patients (injury severity score ≥8) were collected across the pre-hospital (≤2 hours), acute (4-12 hours) and subacute (48-72 hours) post-injury settings. Alongside ex vivo assessments of lipopolysaccharide (LPS)-induced cytokine production by monocytes, neutrophil reactive oxygen species production and phagocytosis, serum concentrations of PGE2 and its scavenger albumin were measured, and the expression of enzymes and receptors involved in PGE2 synthesis and signalling analysed. Leukocytes from trauma patients were treated with cyclooxygenase (COX) inhibitors (indomethacin or NS-398), or the protein kinase A inhibitor H89, to determine whether injury-induced immune suppression could be reversed by targeting the PGE2 pathway. The effect that trauma relevant concentrations of PGE2 had on the anti-microbial functions of neutrophils, monocytes and monocyte-derived macrophages (MDMs) from healthy controls (HC) was examined, as was the effect of PGE2 on efferocytosis. To identify factors that may trigger PGE2 production post-trauma, leukocytes from HC were treated with mitochondrial-derived damage associated molecular patterns (mtDAMPs) and COX-2 expression and PGE2 generation measured. Results: PGE2 concentrations peaked in blood samples acquired ≤2 hours post-injury and coincided with significantly reduced levels of albumin and impaired LPS-induced cytokine production by monocytes. Significantly higher COX-2 and phospholipase A2 expression was detected in neutrophils and/or peripheral blood mononuclear cells isolated from trauma patients. Treatment of patient leukocytes with indomethacin, NS-398 or H89 enhanced LPS-induced cytokine production and neutrophil extracellular trap generation. Exposure to physiological concentrations of PGE2 suppressed the anti-microbial activity of monocytes, neutrophils and MDMs of HC, but did not influence efferocytosis. In a formyl-peptide receptor-1 dependent manner, mtDAMP treatment significantly increased COX-2 protein expression in neutrophils and monocytes, which resulted in increased PGE2 production. Conclusions: Physiological concentrations of PGE2 suppress the anti-microbial activities of neutrophils, monocytes and MDMs. Targeting the PGE2 pathway could be a therapeutic approach by which to enhance innate immune function post-injury. [ABSTRACT FROM AUTHOR] more...- Published
- 2024
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17. Advances in regulation of macrophage polarization by prostaglandin E2.
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LI Wenbo and WAN Cong
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CELL anatomy , *ARACHIDONIC acid , *INFLAMMATORY mediators , *DINOPROSTONE , *SMALL molecules - Abstract
Prostaglandin E2 (PGE2), an arachidonic acid metabolite, is a biologically active lipid small molecule, which was known as an inflammatory mediator previously. Macrophages are important cellular component of intrinsic immune system and the first line of defense against pathogenic invasion. Macrophages are highly plastic and can be simply divided into classically activated Ml type and alternative activated M2 type depending on their morphology and function. In healthy state, these two phenotypes of macrophages are in a dynamic balance to maintain immune homeostasis; when body is stimulated by infection or inflammation, M1/M2 can be converted to each other, thus participating in disease onset and progression and influencing disease regression. It has been shown that PGE2 can regulate macrophage polarization in inflammatory diseases, involving complex mechanisms such as signaling pathways, metabolic processes, and miRNA regulatory networks. Therefore, this paper will briefly summarize mechanism of PGE2 regulation of macrophage polarization and effects of this regulation in inflammatory diseases. [ABSTRACT FROM AUTHOR] more...
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- 2024
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18. Clinical and Radiographic Status and PISF Levels of PGE2 Around Cement and Screw Retained Implants
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Suha Mohammed Aljudaibi, Abdulrahman Ahmed Aseri, Mohammad Abdullah Zayed Alqhtani, Omir Aldowah, Khalid Dhafer S. Alhendi, and Ahmed A. Almeshari
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Crestal bone loss ,Cement-retained ,Dental implants ,Probing depth ,Prostaglandin E2 ,Screw-retained ,Dentistry ,RK1-715 - Abstract
Background: The aim was to assess the peri-implant clinicoradiographic status and prostaglandin E2 (PGE2) levels in peri-implant sulcular fluid (PISF) samples collected from individuals with cement-retained and crew-retained implants. Methods: In this observational study, participants with cement-retained and screw-retained implants were enrolled. A questionnaire was utilized to gather demographic information and assess the educational background of the participants. Peri-implant modified plaque and bleeding indices, probing depth, and crestal bone loss were measured. Subsequently, PISF samples were collected, and corresponding volumes were recorded. Commercial kits employing enzyme-linked immunosorbent assay were employed to quantify PGE2 levels. The sample size was determined, and group comparisons were conducted using the Student t test and the Mann-Whitney U-test. Logistic regression models were constructed to evaluate the correlation between PGE2 levels and clinicoradiographic and demographics. The predefined level of significance was established at P < .05. Results: Sixty-seven participants, consisting of 33 with cement-retained implants and 34 with screw-retained implants, were included in the study. The mean ages for individuals with cement and screw-retained implants were 54.2 ± 8.7 and 58.7 ± 7.4 years, respectively. The majority of participants had completed university-level education. Reportedly, 87.9% and 82.4% of individuals with cement and screw-retained implants, respectively brushed teeth twice daily. No significant differences were observed in clinicoradiographic parameters, PGE2 volume, and levels between cement-retained and screw-retained implants. There was no correlation between PGE2 levels and peri-implant clinicoradiographic parameters among individuals with either cement-retained or screw-retained implants. Conclusions: Cement-retained and screw-retained implants exhibit a consistent peri-implant clinicoradiographic status, accompanied by stable levels of PGE2 in PISF provided oral hygiene maintenance regimens are stringently followed. more...
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- 2024
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19. Gardenia jasminoides fruit extract alleviates non-steroidal anti-inflammatory drug–induced gastropathy in rats
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Rinrada Worapongpaiboon, Kasiphak Kaikaew, Pornpen Werawatganone, Kanjana Somanawat, Nathawadee Lerttanatum, Naruemon Klaikeaw, and Duangporn Werawatganon
- Subjects
Gardenia jasminoides extract ,NSAID-induced gastropathy ,NF-kappa B ,Mucin 5AC ,Inducible nitric oxide synthase ,Prostaglandin E2 ,Other systems of medicine ,RZ201-999 - Abstract
Abstract Background NSAID-induced gastropathy is a health burden that requires effective intervention. Among various prevention options, Gardenia jasminoides fruit extract (GJE) has demonstrated gastroprotective effects through anti-inflammatory pathways with a wide safety margin. However, the detailed molecular mechanisms of GJE regarding mucoprotective and anti-inflammatory effects remained to be explored. Therefore, we investigated the effects of GJE on NSAID-induced gastric injury in rats, focusing on the expression of the protective factors: prostaglandin E2 (PGE2) and mucin 5AC (MUC5AC), and the aggravating factors: inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB). Methods Twenty-four male Sprague–Dawley rats were assigned to three experimental groups (n = 8/group): the control group, the NSAIDs group receiving indomethacin to induce gastric ulcers, and the NSAIDs with GJE pretreatment (NSAIDs + GJE) group. After a two-day experimental period, the stomachs were collected for histopathological examination, immunohistochemical staining, and protein expression analysis in gastric tissue lysates. Results The NSAIDs group exhibited severe neutrophil infiltration with ulcers upon gastric histopathological examination. Pretreatment with GJE attenuated NSAID-induced gastropathy, as evidenced by reduced neutrophil infiltration and decreased ulceration. Immunohistochemical staining and Western blotting demonstrated reduced expressions of PGE2 and MUC5AC, while the expressions of iNOS and NF-κB were increased following NSAID administration. In comparison to the NSAIDs group, the NSAIDs + GJE group exhibited higher expressions of PGE2 and MUC5AC and lower expressions of iNOS and NF-κB, providing evidence of the gastroprotective effects of GJE. Conclusions Pretreatment with GJE alleviated NSAID-induced gastric ulcers by increasing the expression of PGE2 and MUC5AC and decreasing the expression of iNOS and NF-κB. This study contributes to the understanding of the mechanisms by which GJE attenuates NSAID-induced gastropathy. Further studies are required to validate the effect of GJE in clinical settings. more...
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- 2024
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20. Homocysteine aggravates intestinal inflammation through promotion of 5-LOX and COX-2 in IBD
- Author
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Jing Wang, Lin Li, Pingbo Chen, Chiyi He, Xiaoping Niu, and Qiao Mei
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Cysteinyl leukotrienes ,Prostaglandin E2 ,Nuclear factor kappa B ,Inflammatory bowel disease ,Homocysteine ,5-Lipoxygenase ,Medicine - Abstract
Abstract Background Homocysteine (Hcy) is a pro-inflammatory molecule that has the potential to induce oxidative damage to cells and stimulate the release of inflammatory mediators. Hcy has been observed to enhance the production of inflammatory agents in vascular endothelial cells. However, the impact of Hcy on intestinal mucosal inflammation remains largely unexplored. Therefore, the objective of this study was to examine the potential of Hcy to stimulate the synthesis of inflammatory mediators and elucidate the underlying mechanisms in the intestinal mucosa. Methods A total of 99 patients diagnosed with inflammatory bowel disease (IBD) and 10 healthy individuals were included in this study to assess the impact of homocysteine (Hcy) on the levels of leukotriene E4 (LTE4) and prostaglandin E2 (PGE2). The underlying mechanism responsible for the generation of LTE4 and PGE2 induced by Hcy was investigated using colitis rats and Caco-2 cells. 32 Sprague–Dawley rats were categorized into four groups: normal control, TNBS model, normal with Hcy injection, and TNBS model with Hcy injection. The mRNA expressions of 5-LOX, COX-2, and NF-κB were assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Caco-2 cells were subjected to treatment with varying concentrations (10, 20, 50, 100 μmol/L) of Hcy and incubated for different durations (1, 3, 6 h). The alterations in NF-κB activity, as well as the levels of Hcy, LTE4, and PGE2, were measured using enzyme-linked immunosorbent assay (ELISA). Results The excretion of Hcy, LTE4, and PGE2 in urine exhibited significant increases in patients with inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC). In addition, Hcy demonstrated a significant increase in the expression of 5-LOX, COX-2, and NF-κB, as well as elevated levels of LTE4 and PGE2 in rats with colitis. Furthermore, Hcy was found to induce NF-κB activation and nuclear translocation, thereby contributing to the enhanced synthesis of LTE4 and PGE2 in Caco-2 cells. Conclusions Hcy was found to enhance the expression of 5-LOX and COX-2 by activating NF-κB, thereby augmenting the production of LTE4 and PGE2, which ultimately exacerbates colonic inflammation in individuals with inflammatory bowel disease (IBD). more...
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- 2024
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21. Factors associated with insufficient cervical ripening in a controlled-release dinoprostone vaginal delivery system: A single perinatal center retrospective study
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Ayako Takizawa, Youhei Tsunoda, Takashi Matsushima, and Shunji Suzuki
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Cervical ripening ,Dinoprostone vaginal insert ,Induction of labor ,Ineffective factors ,Prostaglandin E2 ,Gynecology and obstetrics ,RG1-991 - Abstract
Objective: In this study, we aimed to evaluate the factors associated with insufficient cervical ripening in a controlled-release dinoprostone vaginal delivery system (Propess). Materials and methods: This retrospective cohort study included 103 pregnant women who used Propess for labor induction. The outcomes were the factors associated with insufficient cervical ripening, defined as a Bishop score ≤6 on the morning after Propess administration. Results: Forty-nine participants had insufficient cervical ripening, and 54 had sufficient cervical ripening. Univariate analysis of these two groups showed that maternal age ≥35 years, early-term delivery (gestational age between 37 and 38 weeks), and Bishop scores at insertion ≤1 were significantly higher in the insufficient cervical ripening group. Multivariate logistic analysis showed that maternal age ≥35 years (adjusted odds ratio: 3.08, 95% confidence interval: 1.29–7.36, p = 0.011) and early-term delivery (adjusted odds ratio: 3.17, 95% confidence interval: 1.23–8.20, p = 0.017) were independent factors associated with poor Propess efficacy. Parity, pre-pregnancy body mass index, body mass index at delivery, and indications for labor induction were not associated with insufficient cervical ripening. Conclusions: In our study, older maternal age and early-term delivery were independent predictors of insufficient cervical ripening with Propess. More effective delivery management can be achieved by considering induction protocols tailored to individual maternal factors for patients with factors associated with poor Propess efficacy. more...
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- 2024
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22. Spinster homolog 2/S1P signaling ameliorates macrophage inflammatory response to bacterial infections by balancing PGE2 production
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Chao Fang, Pan Ren, Yejun He, Yitian Wang, Shuting Yao, Congying Zhao, Xueyong Li, Xi Zhang, Jinqing Li, and Mingkai Li
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Macrophages ,Spinster homolog 2 ,Sphingosine-1-phosphate ,Prostaglandin E2 ,Immunometabolism ,Inflammatory response ,Medicine ,Cytology ,QH573-671 - Abstract
Abstract Background Mitochondria play a crucial role in shaping the macrophage inflammatory response during bacterial infections. Spinster homolog 2 (Spns2), responsible for sphingosine-1-phosphate (S1P) secretion, acts as a key regulator of mitochondrial dynamics in macrophages. However, the link between Spns2/S1P signaling and mitochondrial functions remains unclear. Methods Peritoneal macrophages were isolated from both wild-type and Spns2 knockout rats, followed by non-targeted metabolomics and RNA sequencing analysis to identify the potential mediators through which Spns2/S1P signaling influences the mitochondrial functions in macrophages. Various agonists and antagonists were used to modulate the activation of Spns2/S1P signaling and its downstream pathways, with the underlying mechanisms elucidated through western blotting. Mitochondrial functions were assessed using flow cytometry and oxygen consumption assays, as well as morphological analysis. The impact on inflammatory response was validated through both in vitro and in vivo sepsis models, with the specific role of macrophage-expressed Spns2 in sepsis evaluated using Spns2 flox/flox Lyz2-Cre mice. Additionally, the regulation of mitochondrial functions by Spns2/S1P signaling was confirmed using THP-1 cells, a human monocyte-derived macrophage model. Results In this study, we unveil prostaglandin E2 (PGE2) as a pivotal mediator involved in Spns2/S1P-mitochondrial communication. Spns2/S1P signaling suppresses PGE2 production to support malate-aspartate shuttle activity. Conversely, excessive PGE2 resulting from Spns2 deficiency impairs mitochondrial respiration, leading to intracellular lactate accumulation and increased reactive oxygen species (ROS) generation through E-type prostanoid receptor 4 activation. The overactive lactate-ROS axis contributes to the early-phase hyperinflammation during infections. Prolonged exposure to elevated PGE2 due to Spns2 deficiency culminates in subsequent immunosuppression, underscoring the dual roles of PGE2 in inflammation throughout infections. The regulation of PGE2 production by Spns2/S1P signaling appears to depend on the coordinated activation of multiple S1P receptors rather than any single one. Conclusions These findings emphasize PGE2 as a key effector of Spns2/S1P signaling on mitochondrial dynamics in macrophages, elucidating the mechanisms through which Spns2/S1P signaling balances both early hyperinflammation and subsequent immunosuppression during bacterial infections. more...
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- 2024
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23. Effect of Ganoderma lucidum extract on tumor necrosis factor-alpha and prostaglandin E2 levels in periodontitis model Sprague Dawley rats
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Restian Febi Andini, Dody Novrial, and Haris Budi Widodo
- Subjects
anti-inflammatory ,ganoderma lucidum ,periodontitis ,prostaglandin e2 ,tumor necrosis factor alpha ,Dentistry ,RK1-715 - Abstract
Background: Periodontitis is a chronic multifactorial disease caused by microorganisms such as G-anaerobes in the periodontal tissues. It activates host defense cells and releases inflammatory mediators such as tumor necrosis factor-alpha (TNF-α) and prostaglandin E2 (PGE2). Ganoderma lucidum is a traditional medicinal mushroom with anti-inflammatory effects against various diseases. Biologically, different levels of its active constituents, such as triterpenoids and phenolic compounds, reduce inflammation with various pathways. Furthermore, the constituents inhibit toll-like receptor 4, MyD88 receptors, and the activities of nuclear factor-kappa B, which synthesize TNF-α and PGE2. Purpose: This study aimed to analyze the extent to which G. lucidum extract can reduce TNF-α and PGE2 levels in periodontitis model Sprague Dawley rats. Methods: Thirty Sprague Dawley rats were randomly divided into six groups of five rats. Periodontitis inflammation was induced by the injection of Porphyromonas gingivalis bacteria into intrasulcular gingival incisors in the lower jaw labial section. Grouping was as follows: Group K1 (healthy control); Group K2 (negative control); Group K3 (positive control with doxycycline dose 0.27 mg/kg BW); Group P1 (G. lucidum extract dose 5 mg/kg BW); Group P2 (G. lucidum extract dose 10 mg/kg BW); and Group P3 (G. lucidum extract dose 20 mg/kg BW). Samples were taken from rat gingival tissue and the levels of TNF-α and PGE2 were examined using the enzyme-linked immunosorbent assay method. Data analysis was performed using one-way analysis of variance (ANOVA) with a confidence level of 95% (p < 0.05). Results: The levels of TNF-α and PGE2 were the highest in the K2 group and the lowest in the K1 group. One-way ANOVA showed no significant difference in TNF-α and PGE2 levels between P3 and K1 group. Conclusion: G. lucidum extract can reduce TNF-α and PGE2 levels in Sprague Dawley rats with periodontitis. more...
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- 2024
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24. Leptin‐mediated suppression of lipoprotein lipase cleavage enhances lipid uptake and facilitates lymph node metastasis in gastric cancer
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Jian Xiao, Shuqing Cao, Jiawei Wang, Pengyu Li, Quan Cheng, Xinyi Zhou, Jiacheng Dong, Yuan Li, Xinyu Zhao, Zekuan Xu, and Li Yang
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angiopoietin‐like protein 4 ,leptin ,lipoprotein lipase ,lymph node metastasis ,prostaglandin E2 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Lymph node metastasis (LNM) is the primary mode of metastasis in gastric cancer (GC). However, the precise mechanisms underlying this process remain elusive. Tumor cells necessitate lipid metabolic reprogramming to facilitate metastasis, yet the role of lipoprotein lipase (LPL), a pivotal enzyme involved in exogenous lipid uptake, remains uncertain in tumor metastasis. Therefore, the aim of this study was to investigate the presence of lipid metabolic reprogramming during LNM of GC as well as the role of LPL in this process. Methods Intracellular lipid levels were quantified using oil red O staining, BODIPY 493/503 staining, and flow cytometry. Lipidomics analysis was employed to identify alterations in intracellular lipid composition following LPL knockdown. Protein expression levels were assessed through immunohistochemistry, Western blotting, and enzyme‐linked immunosorbent assays. The mouse popliteal LNM model was utilized to investigate differences in LNM. Immunoprecipitation and mass spectrometry were employed to examine protein associations. In vitro phosphorylation assays and Phos‐tag sodium dodecyl‐sulfate polyacrylamide gel electrophoresis assays were conducted to detect angiopoietin‐like protein 4 (ANGPTL4) phosphorylation. Results We identified that an elevated intracellular lipid level represents a crucial characteristic of node‐positive (N+) GC and further demonstrated that a high‐fat diet can expedite LNM. LPL was found to be significantly overexpressed in N+ GC tissues and shown to facilitate LNM by mediating dietary lipid uptake within GC cells. Leptin, an obesity‐related hormone, intercepted the effect exerted by ANGPTL4/Furin on LPL cleavage. Circulating leptin binding to the leptin receptor could induce the activation of inositol‐requiring enzyme‐1 (IRE1) kinase, leading to the phosphorylation of ANGPTL4 at the serine 30 residue and subsequently reducing its binding affinity with LPL. Moreover, our research revealed that LPL disrupted lipid homeostasis by elevating intracellular levels of arachidonic acid, which then triggered the cyclooxygenase‐2/prostaglandin E2 (PGE2) pathway, thereby promoting tumor lymphangiogenesis. Conclusions Leptin‐induced phosphorylation of ANGPTL4 facilitates LPL‐mediated lipid uptake and consequently stimulates the production of PGE2, ultimately facilitating LNM in GC. more...
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- 2024
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25. Aqueous Extracts of Rhus trilobata Inhibit the Lipopolysaccharide-Induced Inflammatory Response In Vitro and In Vivo.
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Rodríguez-Castillo, Alejandra Jazmín, González-Chávez, Susana Aideé, Portillo-Pantoja, Ismael, Cruz-Hermosillo, Eunice, Pacheco-Tena, César, Chávez-Flores, David, Delgado-Gardea, Ma. Carmen E., Infante-Ramírez, Rocío, Ordaz-Ortiz, José Juan, and Sánchez-Ramírez, Blanca more...
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NON-communicable diseases ,GENE expression ,RHEUMATISM ,LABORATORY rats ,ANTI-inflammatory agents - Abstract
Chronic noncommunicable diseases (NCDs) are responsible for approximately 74% of deaths globally. Medicinal plants have traditionally been used to treat NCDs, including diabetes, cancer, and rheumatic diseases, and are a source of anti-inflammatory compounds. This study aimed to evaluate the anti-inflammatory effects of Rhus trilobata (Rt) extracts and fractions in lipopolysaccharide (LPS)-induced inflammation models in vitro and in vivo. The aqueous extract (RtAE) and five fractions (F2 to F6) were obtained via C18 solid-phase separation and tested in murine LPS-induced J774.1 macrophages. Key inflammatory markers, such as IL-1β, IL-6, TNF-α, and COX-2 gene expression were measured using RT-qPCR, and PGE
2 production was assessed via HPLC-DAD. The in vivo effects were tested in an LPS-induced paw edema model in Wistar rats. Results showed that RtAE at 15 μg/mL significantly decreased IL-1β and IL-6 gene expression in vitro. Fraction F6 further reduced IL-1β, TNF-α, and IL-6 gene expression, COX-2 expression, and PGE2 production. In vivo, F6 significantly reduced LPS-induced paw edema, inflammatory infiltration, and IL-1β and COX-2 protein expression. Chemical characterization of F6 by UPLC/MS-QTOF revealed at least eight compounds with anti-inflammatory activity. These findings support the anti-inflammatory potential of RtAE and F6, reinforcing the medicinal use of Rt. [ABSTRACT FROM AUTHOR] more...- Published
- 2024
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26. Spinster homolog 2/S1P signaling ameliorates macrophage inflammatory response to bacterial infections by balancing PGE2 production.
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Fang, Chao, Ren, Pan, He, Yejun, Wang, Yitian, Yao, Shuting, Zhao, Congying, Li, Xueyong, Zhang, Xi, Li, Jinqing, and Li, Mingkai
- Subjects
- *
PERITONEAL macrophages , *MITOCHONDRIAL dynamics , *LABORATORY rats , *BACTERIAL diseases , *REACTIVE oxygen species , *OXYGEN consumption , *METABOLOMICS - Abstract
Background: Mitochondria play a crucial role in shaping the macrophage inflammatory response during bacterial infections. Spinster homolog 2 (Spns2), responsible for sphingosine-1-phosphate (S1P) secretion, acts as a key regulator of mitochondrial dynamics in macrophages. However, the link between Spns2/S1P signaling and mitochondrial functions remains unclear. Methods: Peritoneal macrophages were isolated from both wild-type and Spns2 knockout rats, followed by non-targeted metabolomics and RNA sequencing analysis to identify the potential mediators through which Spns2/S1P signaling influences the mitochondrial functions in macrophages. Various agonists and antagonists were used to modulate the activation of Spns2/S1P signaling and its downstream pathways, with the underlying mechanisms elucidated through western blotting. Mitochondrial functions were assessed using flow cytometry and oxygen consumption assays, as well as morphological analysis. The impact on inflammatory response was validated through both in vitro and in vivo sepsis models, with the specific role of macrophage-expressed Spns2 in sepsis evaluated using Spns2flox/floxLyz2-Cre mice. Additionally, the regulation of mitochondrial functions by Spns2/S1P signaling was confirmed using THP-1 cells, a human monocyte-derived macrophage model. Results: In this study, we unveil prostaglandin E2 (PGE2) as a pivotal mediator involved in Spns2/S1P-mitochondrial communication. Spns2/S1P signaling suppresses PGE2 production to support malate-aspartate shuttle activity. Conversely, excessive PGE2 resulting from Spns2 deficiency impairs mitochondrial respiration, leading to intracellular lactate accumulation and increased reactive oxygen species (ROS) generation through E-type prostanoid receptor 4 activation. The overactive lactate-ROS axis contributes to the early-phase hyperinflammation during infections. Prolonged exposure to elevated PGE2 due to Spns2 deficiency culminates in subsequent immunosuppression, underscoring the dual roles of PGE2 in inflammation throughout infections. The regulation of PGE2 production by Spns2/S1P signaling appears to depend on the coordinated activation of multiple S1P receptors rather than any single one. Conclusions: These findings emphasize PGE2 as a key effector of Spns2/S1P signaling on mitochondrial dynamics in macrophages, elucidating the mechanisms through which Spns2/S1P signaling balances both early hyperinflammation and subsequent immunosuppression during bacterial infections. [ABSTRACT FROM AUTHOR] more...
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- 2024
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27. Optimizing aspirin dose for colorectal cancer patients through deep phenotyping using novel biomarkers of drug action.
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Patrignani, Paola, Tacconelli, Stefania, Contursi, Annalisa, Piazuelo, Elena, Bruno, Annalisa, Nobili, Stefania, Mazzei, Matteo, Milillo, Cristina, Hofling, Ulrika, Hijos-Mallada, Gonzalo, Sostres, Carlos, and Lanas, Angel more...
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TRANSCRIPTION factors ,LIQUID chromatography-mass spectrometry ,ANTINEOPLASTIC agents ,COLON tumors ,ASPIRIN ,BLOOD platelet aggregation - Abstract
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. [ABSTRACT FROM AUTHOR] more...
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- 2024
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28. Roles of Toll-like Receptor Signaling in Inflammatory Bone Resorption.
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Tominari, Tsukasa, Matsumoto, Chiho, Tanaka, Yuki, Shimizu, Kensuke, Takatoya, Masaru, Sugasaki, Moe, Karouji, Kento, Kasuga, Urara, Miyaura, Chisato, Miyata, Shinji, Itoh, Yoshifumi, Hirata, Michiko, and Inada, Masaki more...
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- *
BONE resorption , *PATTERN perception receptors , *NF-kappa B , *TOLL-like receptors , *ALVEOLAR process - Abstract
Simple Summary: Toll-like receptor (TLR) signaling contributes to the pathogenesis of inflammatory oral diseases, such as periodontal disease by stimulating osteoclast differentiation and function. Recent reports suggest that various components from bacteria, viruses, and autologous cells act as TLR ligands. Lipopolysaccharide (LPS), a TLR4 ligand, induces osteoclast differentiation and bone resorption; however, blocking PGE2 synthesis or antagonizing PGE2 receptor signaling abrogates LPS-induced inflammatory bone resorption. In addition, other ligands for TLR2/1, TLR2/6 and TLR3 facilitate PGE2 production, leading to osteoclastic bone resorption. This review introduces the latest findings regarding the relationship between TLR signaling pathways and inflammatory bone resorption. Toll-like receptors (TLRs) are pattern recognition receptors expressed in immune cells, including neutrophils, macrophages, and dendritic cells. Microbe-associated molecular patterns, including bacterial components, membranes, nucleic acids, and flagella are recognized by TLRs in inflammatory immune responses. Periodontal disease is an inflammatory disease known to cause local infections associated with gingival inflammation, subsequently leading to alveolar bone resorption. Prostaglandin E2 (PGE2) is a key mediator of TLR-induced inflammatory bone resorption. We previously reported that membrane-bound PGE synthase (mPGES-1)-deficient mice failed to induce bone resorption by lipopolysaccharide (LPS), a major pathogenic factor involved in periodontal bone resorption. Further experiments exploring specific pathogen-promoting osteoclast differentiation revealed that various TLR ligands induced osteoclast differentiation in a co-culture model. The ligands for TLR2/1, TLR2/6, TLR3, and TLR5, as well as TLR4, induce osteoclast differentiation associated with the production of PGE2 and the receptor activator of nuclear factor-kappa B ligand (RANKL), an inevitable inducer of osteoclast differentiation in osteoblasts. In vivo, local injection of TLR ligands, including TLR2/1, TLR2/6, and TLR3, resulted in severe alveolar bone resorption. This review summarizes the latest findings on TLR-mediated osteoclast differentiation and bone resorption in inflammatory diseases, such as periodontal diseases. [ABSTRACT FROM AUTHOR] more...
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- 2024
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29. Pulmonary surfactant and prostaglandin E2 in airway smooth muscle relaxation of human and male guinea pigs.
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Hanusrichterova, J., Kolomaznik, M., Barosova, R., Adamcakova, J., Mokra, D., Mokry, J., Skovierova, H., Kelly, M. M., de Heuvel, E., Wiehler, S., Proud, D., Shen, H., Mukherjee, P. G., Amrein, M. W., and Calkovska, A. more...
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ATOMIC force microscopy , *PULMONARY surfactant , *SMOOTH muscle , *GUINEA pigs , *DINOPROSTONE - Abstract
Pulmonary surfactant serves as a barrier to respiratory epithelium but can also regulate airway smooth muscle (ASM) tone. Surfactant (SF) relaxes contracted ASM, similar to β2‐agonists, anticholinergics, nitric oxide, and prostanoids. The exact mechanism of surfactant relaxation and whether surfactant relaxes hyperresponsive ASM remains unknown. Based on previous research, relaxation requires an intact epithelium and prostanoid synthesis. We sought to examine the mechanisms by which surfactant causes ASM relaxation. Organ bath measurements of isometric tension of ASM of guinea pigs in response to exogenous surfactant revealed that surfactant reduces tension of healthy and hyperresponsive tracheal tissue. The relaxant effect of surfactant was reduced if prostanoid synthesis was inhibited and/or if prostaglandin E2‐related EP2 receptors were antagonized. Atomic force microscopy revealed that human ASM cells stiffen during contraction and soften during relaxation. Surfactant softened ASM cells, similarly to the known bronchodilator prostaglandin E2 (PGE2) and the cell softening was abolished when EP4 receptors for PGE2 were antagonized. Elevated levels of PGE2 were found in cultures of normal human bronchial epithelial cells exposed to pulmonary surfactant. We conclude that prostaglandin E2 and its EP2 and EP4 receptors are likely involved in the relaxant effect of pulmonary surfactant in airways. [ABSTRACT FROM AUTHOR] more...
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- 2024
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30. Prostaglandin E2 Induces YAP1 and Agrin Through EP4 in Neonatally-Derived Islet-1+ Stem Cells.
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Hughes, Lorelei, Lopez, Larry V., and Kearns-Jonker, Mary
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TRANSCRIPTION factors , *EXTRACELLULAR matrix proteins , *STEM cells , *EXTRACELLULAR matrix , *MATRIX metalloproteinases - Abstract
Prostaglandin E2 (PGE2) has recently gained attention in the field of regenerative medicine because of the beneficial effects of this molecule on stem cell proliferation and migration. Furthermore, PGE2 has the ability to mitigate immune rejection and fibrosis. In the colon and kidney, PGE2 induces YAP1, a transcription factor critical for cardiac regeneration. Establishing a similar connection in stem cells that can be transplanted in the heart could lead to the development of more effective therapeutics. In this report, we identify the effects of PGE2 on neonatal Islet-1+ stem cells. These stem cells synthesize PGE2, which functions by stimulating the transcription of the extracellular matrix protein Agrin. Agrin upregulates YAP1. Consequently, both YAP1 and Agrin are induced by PGE2 treatment. Our study shows that PGE2 upregulated the expression of both YAP1 and Agrin in Islet-1+ stem cells through the EP4 receptor and stimulated proliferation using the same mechanisms. PGE2 administration further elevated the expression of stemness markers and the matrix metalloproteinase MMP9, a key regulator of remodeling in the extracellular matrix post-injury. The expression of PGE2 in neonatal Islet-1+ cells is a factor which contributes to improving the functional efficacy of these cells for cardiac repair. [ABSTRACT FROM AUTHOR] more...
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- 2024
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31. Effect of Ganoderma lucidum extract on tumor necrosis factoralpha and prostaglandin E2 levels in periodontitis model Sprague Dawley rats.
- Author
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Andini, Restian Febi, Novrial, Dody, and Widodo, Haris Budi
- Subjects
SPRAGUE Dawley rats ,PERIODONTITIS ,GANODERMA lucidum ,DINOPROSTONE ,TUMOR necrosis factors ,ENZYME-linked immunosorbent assay ,NF-kappa B ,PROSTAGLANDIN receptors - Abstract
Background: Periodontitis is a chronic multifactorial disease caused by microorganisms such as G-anaerobes in the periodontal tissues. It activates host defense cells and releases inflammatory mediators such as tumor necrosis factor-alpha (TNF-α) and prostaglandin E2 (PGE2). Ganoderma lucidum is a traditional medicinal mushroom with anti-inflammatory effects against various diseases. Biologically, different levels of its active constituents, such as triterpenoids and phenolic compounds, reduce inflammation with various pathways. Furthermore, the constituents inhibit toll-like receptor 4, MyD88 receptors, and the activities of nuclear factor-kappa B, which synthesize TNF-α and PGE2. Purpose: This study aimed to analyze the extent to which G. lucidum extract can reduce TNF-α and PGE2 levels in periodontitis model Sprague Dawley rats. Methods: Thirty Sprague Dawley rats were randomly divided into six groups of five rats. Periodontitis inflammation was induced by the injection of Porphyromonas gingivalis bacteria into intrasulcular gingival incisors in the lower jaw labial section. Grouping was as follows: Group K1 (healthy control); Group K2 (negative control); Group K3 (positive control with doxycycline dose 0.27 mg/kg BW); Group P1 (G. lucidum extract dose 5 mg/kg BW); Group P2 (G. lucidum extract dose 10 mg/kg BW); and Group P3 (G. lucidum extract dose 20 mg/kg BW). Samples were taken from rat gingival tissue and the levels of TNF-α and PGE2 were examined using the enzyme-linked immunosorbent assay method. Data analysis was performed using one-way analysis of variance (ANOVA) with a confidence level of 95% (p < 0.05). Results: The levels of TNF-α and PGE2 were the highest in the K2 group and the lowest in the K1 group. One-way ANOVA showed no significant difference in TNF-α and PGE2 levels between P3 and K1 group. Conclusion: G. lucidum extract can reduce TNF-α and PGE2 levels in Sprague Dawley rats with periodontitis. [ABSTRACT FROM AUTHOR] more...
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- 2024
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32. Determinants of joint effusion in tarsocrural osteochondrosis of yearling Standardbred horses.
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Bertuglia, Andrea, Pallante, Marcello, Pagliara, Eleonora, Valle, Daniela, Bergamini, Lara, Bollo, Enrico, Bullone, Michela, and Riccio, Barbara
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JOINT diseases ,JOINT instability ,SYNOVIAL fluid ,EXTRACELLULAR matrix ,OSTEOCHONDROSIS - Abstract
Tarsocrural osteochondrosis (OCD) is a developmental orthopedic disease commonly affecting young Standardbreds, with different fragment localization and size. Clinically, it is characterized by variable synovial effusion in the absence of lameness, whose determinants are ill-defined. We hypothesized that localization and physical characteristics of the osteochondral fragments like dimensions, multifragmentation, and instability influence joint effusion and correlate with synovial markers of cartilage degradation and inflammation. Clinical data, synovial fluid and intact osteochondral fragments were collected from 79 Standardbred horses, aged between 12 and 18  months, operated for tarsocrural OCD. The severity of tarsocrural joint effusion was assessed semiquantitatively. The osteochondral fragment site was defined radiographically at the distal intermediate ridge of the tibia (DIRT), medial malleolus (MM) of the tibia, and/or lateral trochlear ridge (LTR) of the talus. Size, stability, and arthroscopic appearance (unique or multi-fragmented aspect) of the fragments were determined intra-operatively. Synovial concentrations of C-terminal cross-linked telopeptides of type II collagen (CTX-II), leukotriene B4 (LTB4), and prostaglandin E2 (PGE2) were quantified. Tarsocrural synovial effusion was significantly affected by localization and stability of the fragments, with MMlocated and unstable fragments being associated with highest joint effusion. Concentrations of CTX-II, LTB4, and PGE2 positively correlated with the severity of synovial effusion. This study underlines characteristics of the osteochondral fragments determining higher synovial effusion in OCD-affected tarsocrural joints and suggests both inflammation and extra-cellular matrix degradation are active processes in OCD pathology. [ABSTRACT FROM AUTHOR] more...
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- 2024
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33. Oxytocin and vaginal dinoprostone in labor induction: A systematic review and meta‐analysis.
- Author
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Chang, Ting‐An, Li, Yi‐Rong, and Ding, Dah‐Ching
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INDUCED labor (Obstetrics) , *OXYTOCIN , *DELIVERY (Obstetrics) , *RANDOM effects model , *CESAREAN section - Abstract
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. Synopsis: Labor induction medication systemic review and meta‐analysis. [ABSTRACT FROM AUTHOR] more...
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- 2024
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34. Effect of curcumin on formalin-induced muscle pain in male rats: role of local cyclooxygenase system.
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Naqshbandi, Nabat, Tamaddonfard, Esmaeal, Erfanparast, Amir, and Soltanalinejad-Taghiabad, Farhad
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CURCUMIN ,MYALGIA ,CYCLOOXYGENASES ,PAIN management ,SKELETAL muscle - Abstract
Investigating the mechanisms responsible for pain processing of natural and synthetic chemical compounds is necessary to optimize pain management. Curcumin (Cur), the active ingredient of turmeric, exhibits potent analgesic and anti-inflammatory properties by employing multiple mechanisms at the local peripheral, spinal and supra-spinal levels. This study was aimed to investigate the effect of oral administration of Cur on muscle pain induced by intramuscular (IM) injection of formalin. To explore the possible local mechanisms, a cyclooxygenase (COX) inhibitor, diclofenac (Dic) and a COX product, prostaglandin E
2 (PGE2 ), were applied. The IM injection of formalin (25.00 µL, 2.50%) into the gastrocnemius muscle induced two distinct phases of hind leg flinching. A short-lasting (10 min) hind leg lifting was observed following IM injection of PGE2 (2 µg kg-1 , 25.00 µL). Oral administration of Cur (25.00 and 100 mg kg-1 ) and IM injection of 40.00 µg kg-1 Dic attenuated formalin and PGE2 induced nociceptive behaviors. Contra-lateral IM injection of Dic did not change muscle pain induced by ipsilateral IM injection of formalin and PGE2 . The second phase of formalin induced flinching as well as PGE2 evoked lifting were more suppressed when 40.00 µg kg-1 Dic and 100 mg kg-1 Cur were used together. Locomotor activity was not changed by the above-mentioned treatments. It was concluded that the reducing effect of muscle pain of Cur might be related to the local inhibition of COX. [ABSTRACT FROM AUTHOR] more...- Published
- 2024
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- View/download PDF
35. Potential Human Health Benefits of Phaseolus vulgaris L. var Venanzio: Effects on Cancer Cell Growth and Inflammation.
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Bernardi, Clizia, Cappellucci, Giorgio, Baini, Giulia, Aloisi, Anna Maria, Finetti, Federica, and Trabalzini, Lorenza
- Abstract
It is widely recognized that foods, biodiversity, and human health are strongly interconnected, and many efforts have been made to understand the nutraceutical value of diet. In particular, diet can affect the progression of intestinal diseases, including inflammatory bowel disease (IBD) and intestinal cancer. In this context, we studied the anti-inflammatory and antioxidant activities of extracts obtained from a local endangered variety of Phaseolus vulgaris L. (Fagiola di Venanzio, FV). Using in vitro intestinal cell models, we evaluated the activity of three different extracts: soaking water, cooking water, and the bioaccessible fraction obtained after mimicking the traditional cooking procedure and gastrointestinal digestion. We demonstrated that FV extracts reduce inflammation and oxidative stress prompted by interleukin 1β through the inhibition of cyclooxygenase 2 expression and prostaglandin E2 production and through the reduction in reactive oxygen species production and NOX1 levels. The reported data outline the importance of diet in the prevention of human inflammatory diseases. Moreover, they strongly support the necessity to safeguard local biodiversity as a source of bioactive compounds. [ABSTRACT FROM AUTHOR] more...
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- 2024
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36. Prostaglandin pathways in equine myometrium regulations: endometrosis progression
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Katarzyna K. Piotrowska-Tomala, Anna Z. Szóstek-Mioduchowska, Ewa M. Drzewiecka, Agnieszka W. Jonczyk, Anna Wójtowicz, Michał H. Wrobel, Graca Ferreira-Dias, and Dariusz J. Skarzynski
- Subjects
prostaglandin E2 ,prostaglandin F2α ,contractions ,myometrium ,mare ,endometrosis ,Veterinary medicine ,SF600-1100 - Abstract
IntroductionProstaglandins (PG) are important regulators of the myometrial contractility in mammals. Endometrosis, a condition characterized by morphological changes in the equine endometrium, also affects endometrial secretory function. However, it remains unclear whether and how endometrosis affects myometrial function.MethodsThis study investigated: (i) mRNA transcription of genes encoding specific enzymes responsible for PG synthesis, such as prostaglandin—endoperoxide synthase (PTGS2), PGE2 synthase (PTGES), PGF2α synthase (PTGFS) and PG receptors: PGE2 receptors (PTGER1- 4), and PGF2α receptor (PTGFS) in equine myometrium and, (ii) the effects of PGE2 and PGF2α on myometrial contractile activity, during endometrosis in mares. The myometria used in experiments 1 and 2 were collected from mares in the mid-luteal (n = 23) and follicular (n = 20) phases of the estrous cycle, according to the histological classification of the endometrium (Kenney and Doig categories I, IIA, IIB, and III).ResultsIn experiment 1, changes in mRNA transcription of PG synthase or PG receptors in the myometrium during the course of endometrosis were determined using qPCR. During the mid-luteal phase, myometrial mRNA transcription of PTGES increased in mares with endometrial category IIB compared to category I. However, myometrial mRNA transcription of PTGER1 decreased during the progression of endometrosis compared to category I. During the follicular phase, mRNA transcription of PTGER1 and PTGER2 increased in mares with endometrial categories III or IIA, respectively. In addition, mRNA transcription of PTGFS increased in mares with endometrium category IIA compared to category I. In experiment 2, the force of myometrial contractions was measured using an isometric concentration transducer. In the follicular phase, PGE2 decreased the force of contractions in mares with endometrial categories IIA, IIB, and III compared to the respective control groups. Prostaglandin F2α increased the force of myometrial contractions in mares with category IIA endometrium, whereas it decreased in category IIB compared to the respective control groups.DiscussionWe concluded that in the progression of endometrosis there are changes in the myometrial transcription of mRNA encoding PG synthases and receptors, particularly PTGER1 and PTGER2. Mares with endometrosis had abnormal myometrial contractile responses to PG. These findings suggest that myometrial function may be compromised during the progression of endometrosis. more...
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- 2024
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37. Cyclooxygenase-2/prostaglandin E2 pathway orchestrates the replication of infectious bronchitis virus in chicken tracheal explants
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Motamed Elsayed Mahmoud, Ahmed Ali, Muhammad Farooq, Ishara M. Isham, Sufna M. Suhail, Heshanthi Herath-Mudiyanselage, Ryan Rahimi, and Mohamed Faizal Abdul-Careem
- Subjects
infectious bronchitis virus ,tracheal organ culture ,cyclooxygenase 2 ,prostaglandin E2 ,selective cyclooxygenase-2 inhibitor ,prostaglandin receptor antagonists ,Microbiology ,QR1-502 - Abstract
ABSTRACT In this study, we investigated the localized pathogenesis of infectious bronchitis virus (IBV) in chicken tracheal organ cultures (TOCs), focusing on the role of inducible cyclooxygenase (COX-2). Two divergent IBV strains, respiratory Connecticut (Conn) A5968 and nephropathogenic Delmarva (DMV)/1639, were studied at 6, 12, 24, and 48 hours post-infection (hpi). Various treatments including exogenous prostaglandin (PGE)2, a selective COX-2 antagonist (SC-236), and inhibitors of PGE2 receptors and Janus kinase (JAK) were administered. IBV genome load and antigen expression were quantified using real-time quantitative PCR and immunohistochemistry. COX-2, interferon (IFN)-α, IFN-β, interleukin (IL)−1β, IL-6, and inducible nitric oxide synthase (iNOS) expressions were measured, along with PGE2 and COX-2 concentrations. IBV genome load and protein expression peaked at 12 and 24 hpi, respectively. Conn A5968-infected TOCs exhibited continuous COX-2 expression for up to 24 hpi, extended PGE2 production up to 48 hpi, and reduced inflammatory cytokine expression. In contrast, DMV/1639-infected TOCs displayed heightened inflammatory cytokine expression, brief COX-2 expression, and PGE2 production. Treatment with IFN-γ, SC-236, PGE2 receptor inhibitors, or JAK inhibitors reduced IBV infection and lesion scores, whereas exogenous PGE2 or IFN-γ pretreatment with a JAK-2 inhibitor augmented infection. These findings shed light on the innate immune regulation of IBV infection in the trachea, highlighting the involvement of the COX-2/PGE2 pathway.IMPORTANCEUnderstanding the localized pathogenesis of infectious bronchitis virus (IBV) within the trachea of chickens is crucial for developing effective control strategies against this prevalent poultry pathogen. This study sheds light on the role of inducible cyclooxygenase (COX-2) and prostaglandin (PGE)2 in IBV pathogenesis using chicken tracheal organ culture (TOC) models. The findings reveal distinct patterns of COX-2 expression, PGE2 production, and immune responses associated with different IBV strains, highlighting the complexity of host-virus interactions. Furthermore, the identification of specific inhibitors targeting the COX-2/PGE2 pathway and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway provides potential therapeutic avenues for mitigating IBV infection in poultry. Overall, this study contributes to our understanding of the innate immune regulation of IBV infection within the trachea, laying the groundwork for the development of targeted interventions to control IBV outbreaks in poultry populations. more...
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- 2024
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38. Distinct etiology of chronic inflammation – implications on degenerative diseases and cancer therapy
- Author
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Krishna Rao Maddipati
- Subjects
unalamation ,cancer etiology ,chronic inflammation ,acute inflammation ,prostaglandin E2 ,epoxy PUFA ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Acute inflammation is elicited by lipid and protein mediators in defense of the host following sterile or pathogen-driven injury. A common refrain is that chronic inflammation is a result of incomplete resolution of acute inflammation and behind the etiology of all chronic diseases, including cancer. However, mediators that participate in inflammation are also essential in homeostasis and developmental biology but without eliciting the clinical symptoms of inflammation. This non-inflammatory physiological activity of the so called ‘inflammatory’ mediators, apparently under the functional balance with anti-inflammatory mediators, is defined as unalamation (un-ala-mation). Inflammation in the absence of injury is a result of perturbance in unalamation due to a decrease in the anti-inflammatory mediators rather than an increase in the inflammatory mediators and leads to chronic inflammation. This concept on the etiology of chronic inflammation suggests that treatment of chronic diseases is better achieved by stimulating the endogenous anti-inflammatory mediators instead of inhibiting the ‘inflammatory’ mediator biosynthesis with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Furthermore, both ‘inflammatory’ and anti-inflammatory mediators are present at higher concentrations in the tumor microenvironment compared to normal tissue environments. Since cancer is a proliferative disorder rather than a degenerative disease, it is proposed that heightened unalamation, rather than chronic inflammation, drives tumor growth. This understanding helps explain the inefficacy of NSAIDs as anticancer agents. Finally, inhibition of anti-inflammatory mediator biosynthesis in tumor tissues could imbalance unalamation toward local acute inflammation triggering an immune response to restore homeostasis and away from tumor growth. more...
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- 2024
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39. IL-13–associated epithelial remodeling correlates with clinical severity in nasal polyposis
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Kotas, Maya E, Patel, Neil N, Cope, Emily K, Gurrola, Jose G, Goldberg, Andrew N, Pletcher, Steven D, Seibold, Max A, Moore, Camille M, and Gordon, Erin D
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Genetics ,Prevention ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Humans ,Interleukin-13 ,Nasal Polyps ,Rhinitis ,Interleukin-17 ,Dinoprostone ,Sinusitis ,Chronic Disease ,Nasal Mucosa ,Chronic rhinosinusitis ,nasal polyposis ,type 2 inflam-mation ,endotype ,IL-13 ,prostaglandin E2 ,epithelial remodeling ,type 2 inflammation ,Immunology ,Allergy - Abstract
BackgroundEpithelial remodeling is a histopathologic feature of chronic inflammatory airway diseases including chronic rhinosinusitis (CRS). Cell-type shifts and their relationship to CRS endotypes and severity are incompletely described.ObjectiveWe sought to understand the relationship of epithelial cell remodeling to inflammatory endotypes and disease outcomes in CRS.MethodsUsing cell-type transcriptional signatures derived from epithelial single-cell sequencing, we analyzed bulk RNA-sequencing data from sinus epithelial brushings obtained from patients with CRS with and without nasal polyps in comparison to healthy controls.ResultsThe airway epithelium in nasal polyposis displayed increased tuft cell transcripts and decreased ciliated cell transcripts along with an IL-13 activation signature. In contrast, CRS without polyps showed an IL-17 activation signature. IL-13 activation scores were associated with increased tuft cell, goblet cell, and mast cell scores and decreased ciliated cell scores. Furthermore, the IL-13 score was strongly associated with a previously reported activated ("polyp") tuft cell score and a prostaglandin E2 activation signature. The Lund-Mackay score, a computed tomographic metric of sinus opacification, correlated positively with activated tuft cell, mast cell, prostaglandin E2, and IL-13 signatures and negatively with ciliated cell transcriptional signatures.ConclusionsThese results demonstrate that cell-type alterations and prostaglandin E2 stimulation are key components of IL-13-induced epithelial remodeling in nasal polyposis, whereas IL-17 signaling is more prominent in CRS without polyps, and that clinical severity correlates with the degree of IL-13-driven epithelial remodeling. more...
- Published
- 2023
40. Sudachitin Reduces Inflammatory Mediator Expression in Toll-Like Receptor 2 Ligand-Stimulated Human Dental Pulp Cells
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Mieda, Katsuhiro, Nakanishi, Tadashi, Kuramoto, Hitomi, Hosokawa, Yoshitaka, Hosokawa, Ikuko, Takegawa, Daisuke, and Hosaka, Keiichi
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- 2024
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41. Clinical observation of Tuina plus electroacupuncture for migraine due to liver-Yang hyperactivity
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- 2024
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42. Prostaglandin E2 depolarises sensory axons in vitro in an ANO1 and Nav1.8 dependent manner
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Georgios Kimourtzis, Natasha Rangwani, Bethan J. Jenkins, Siddharth Jani, Peter A. McNaughton, and Ramin Raouf
- Subjects
Microfluidic cultures ,Dorsal root ganglia neurons ,Prostaglandin E2 ,Inflammation ,Pain ,Sodium channels ,Medicine ,Science - Abstract
Abstract Prostaglandin E2 (PGE2) is a major contributor to inflammatory pain hyperalgesia, however, the extent to which it modulates the activity of nociceptive axons is incompletely understood. We developed and characterized a microfluidic cell culture model to investigate sensitisation of the axons of dorsal root ganglia neurons. We show that application of PGE2 to fluidically isolated axons leads to sensitisation of their responses to depolarising stimuli. Interestingly the application of PGE2 to the DRG axons elicited a direct and persistent spiking activity propagated to the soma. Both the persistent activity and the membrane depolarisation in the axons are abolished by the EP4 receptor inhibitor and a blocker of cAMP synthesis. Further investigated into the mechanisms of the spiking activity showed that the PGE2 evoked depolarisation was inhibited by Nav1.8 sodium channel blockers but was refractory to the application of TTX or zatebradine. Interestingly, the depolarisation of axons was blocked by blocking ANO1 channels with T16Ainh-A01. We further show that PGE2-elicited axonal responses are altered by the changes in chloride gradient within the axons following treatment with bumetanide a Na-K-2Cl cotransporter NKCC1 inhibitor, but not by VU01240551 an inhibitor of potassium-chloride transporter KCC2. Our data demonstrate a novel role for PGE2/EP4/cAMP pathway which culminates in a sustained depolarisation of sensory axons mediated by a chloride current through ANO1 channels. Therefore, using a microfluidic culture model, we provide evidence for a potential dual function of PGE2 in inflammatory pain: it sensitises depolarisation-evoked responses in nociceptive axons and directly triggers action potentials by activating ANO1 and Nav1.8 channels. more...
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- 2024
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43. Magnesium malate-modified calcium phosphate bone cement promotes the repair of vertebral bone defects in minipigs via regulating CGRP
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Hailiang Xu, Fang Tian, Youjun Liu, Renfeng Liu, Hui Li, Xinlin Gao, Cheng Ju, Botao Lu, Weidong Wu, Zhiyuan Wang, Lei Zhu, Dingjun Hao, and Shuaijun Jia
- Subjects
Calcium phosphate cement ,Magnesium malate ,Bone defect ,Calcitonin gene-related peptide ,Prostaglandin E2 ,Osteogenesis ,Biotechnology ,TP248.13-248.65 ,Medical technology ,R855-855.5 - Abstract
Abstract Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair. more...
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- 2024
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44. Enhanced therapeutic effects of apoptotic cell‐conditioned mesenchymal stem cells in lupus‐prone MRL/lpr mice
- Author
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Zhuoya Zhang, Yiyuan Cui, Saisai Huang, Weilin Liu, Chen Chen, Xuebing Feng, Dandan Wang, and Lingyun Sun
- Subjects
apoptotic cells ,mesenchymal stem cells ,precondition ,prostaglandin E2 ,systemic lupus erythematosus ,Immunologic diseases. Allergy ,RC581-607 ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Apoptotic cell‐conditioned mesenchymal stem cells (AC‐MSCs) exhibit stronger T cell suppressive ability via cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2); however, whether AC‐MSCs exhibit enhanced therapeutic effects on systemic lupus erythematosus (SLE) remains unknown. Methods Splenocytes from MRL/MPJ‐Faslpr (MRL/lpr) mice were cocultured with AC‐MSCs, and the proportion of plasma cells was determined by flow cytometry. MSCs, AC‐MSCs, COX2 knockdown MSCs, and COX2 knockdown AC‐MSCs were infused into MRL/lpr mice (n = 10/group). Survival rates and lupus symptoms, including proteinuria, kidney injury, renal immune complex deposition, and autoantibody production, were assessed. Additionally, the number of plasma cells and serum levels of inflammatory cytokines were measured. Results The AC‐MSCs significantly inhibited plasma cells via PGE2 after 24 h coculture in vitro, whereas MSCs did not. In the MRL/lpr mice, AC‐MSC treatment led to a significantly higher survival rate than phosphate‐buffered saline (PBS) treatment (90% vs. 50%, p more...
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- 2024
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45. Effects of grain intervention on hypothalamic function and the metabolome of blood and milk in dairy cows
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Limei Lin, Kaizhen Guo, Huiting Ma, Jiyou Zhang, Zheng Lai, Weiyun Zhu, and Shengyong Mao
- Subjects
Blood ,Grain-based diet ,Hypothalamus ,Metabolomics ,Milk ,Prostaglandin E2 ,Animal culture ,SF1-1100 ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Background The hypothalamus plays a crucial role in the health and productivity of dairy cows, yet studies on its functionality and its impact on peripheral circulation in these animals are relatively scarce, particularly regarding dietary interventions. Therefore, our study undertook a comprehensive analysis, incorporating both metabolomics and transcriptomics, to explore the effects of a grain-based diet on the functionality of the hypothalamus, as well as on blood and milk in dairy cows. Results The hypothalamic metabolome analysis revealed a significant reduction in prostaglandin E2 (PGE2) level as a prominent response to the grain-based diet introduction. Furthermore, the hypothalamic transcriptome profiling showed a notable upregulation in amino acid metabolism due to the grain-based diet. Conversely, the grain-based diet led to the downregulation of genes involved in the metabolic pathway from lecithin to PGE2, including phospholipase A2 (PLA2G4E, PLA2G2A, and PLA2G12B), cyclooxygenase-2 (COX2), and prostaglandin E synthase (PTGES). Additionally, the plasma metabolome analysis indicated a substantial decrease in the level of PGE2, along with a decline in adrenal steroid hormones (tetrahydrocortisol and pregnenolone) following the grain-based diet introduction. Analysis of the milk metabolome showed that the grain-based diet significantly increased uric acid level while notably decreasing PGE2 level. Importantly, PGE2 was identified as a critical metabolic marker in the hypothalamus, blood, and milk in response to grain intervention. Correlation analysis demonstrated a significant correlation among metabolic alterations in the hypothalamus, blood, and milk following the grain-based diet. Conclusions Our findings suggest a potential link between hypothalamic changes and alterations in peripheral circulation resulting from the introduction of a grain-based diet. more...
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- 2024
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46. Effect of quercetin against pilocarpine-induced epilepsy in mice
- Author
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Waleed K. Abdulsahib and Mohanad Y. Al-Radeef
- Subjects
epilepsy ,interleukin 1 beta ,pilocarpine ,prostaglandin e2 ,quercetin ,Therapeutics. Pharmacology ,RM1-950 ,Pharmacy and materia medica ,RS1-441 - Abstract
Globally, an estimated 50 million people are affected by epilepsy, a persistent, noncommunicable neurological ailment. Quercetin (QR) is a prevalent flavonoid substance extensively dispersed throughout agricultural life. In a pilocarpine (PILO)-induced epilepsy model in mice, this investigation aimed to determine whether QR has an antiepileptic effect and explore its putative mechanism of action. Fifty mice were allocated into seven groups, with six in every group. The first group received physiological saline, the second group was given diazepam (1 mg/kg), and four groups were administered QR at 50, 100, 150, and 200 mg/kg, respectively. The seventh group (the induction group) received normal saline. After 30 min, all groups were injected intraperitoneally with PILO. The impact of QR on motor coordination was assessed using the rotarod test, while measures such as latency to first seizure, generalized tonic-clonic seizures (GTCS), number of convulsions, and mortality were recorded. Serum samples were collected through the retro-orbital route to measure prostaglandin E2 (PGE2) and interleukin 1 beta (IL-1β) levels. QR showed no significant difference in motor impairment, but increased duration until the initial seizure occurred and declined the mortality rate, duration of GTCS, and incidence of convulsions. All doses of QR significantly reduced PGE2 levels (P ≤ 0.05). However, QR’s effect on IL-1β reduction was statistically insignificant (P > 0.05). QR’s capacity to inhibit PILO-induced epilepsy by decreasing IL-1 and PGE2 levels is supported by this study. The results of this work indicate that QR could have a function to treat acute epilepsy. more...
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- 2024
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47. Comparison of the efficacy of aescin and diclofenac sodium in the management of postoperative sequelae and their effect on salivary Prostaglandin E2 and serum C–reactive protein levels after surgical removal of impacted mandibular third molar: a randomized, double-blind, controlled clinical trial. [version 3; peer review: 2 approved]
- Author
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Anuroop Singhai, Rajanikanth Kambala, and Nitin Bhola
- Subjects
Study Protocol ,Articles ,Aescin ,Diclofenac ,pain ,swelling ,C-reactive protein ,prostaglandin E2 ,third molar - Abstract
Introduction Surgical removal of an impacted third molar is one of the most common oral surgical procedures performed in dental offices. The postoperative phase is often associated with severe inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) are usually prescribed to manage postoperative discomfort. NSAIDs have been associated with gastrointestinal bleeding, renal function disturbances, and platelet count reductions. Thus, the present study demonstrates the utility of aescin in managing postoperative discomfort after the surgical removal of impacted mandibular third molars. This study aimed to correlate and compare the impact of aescin and diclofenac on salivary PGE2 levels and serum C-reactive protein levels after surgical extraction of the mandibular third molar. The study will also evaluate and compare the effectiveness of individual drug therapy in managing postoperative pain, swelling and mouth opening. Methods The planned study is a single-center, double-blind, randomized, parallel, prospective clinical trial. Each patient will be prescribed either diclofenac sodium 150 mg/day or aescin (escin) 120 mg/day to be taken orally in divided doses for five days after surgically removing the impacted mandibular third molar. Pain will be assessed using a visual analog scale. Facial swelling and mouth opening will be recorded using a metric scale with standardized reference points. ELISA (enzyme-linked immunosorbent assay (ELISA) will be employed to measure salivary Prostaglandin E2 and serum C–reactive protein levels. All parameters will be recorded preoperatively (T0) on the second postoperative day (T1) and fifth postoperative day (T2). Conclusion The proposed study is expected to show a clinically acceptable response to the administration of aescin for the management of postoperative discomfort compared to diclofenac sodium after third molar surgery. The proposed study is expected to positively manipulate the levels of salivary Prostaglandin E2 and serum C–reactive protein, which are reliable inflammatory markers. The outcome of this study may provide an efficacious and safe alternative to conventional nonsteroidal anti-inflammatory drugs for managing postoperative discomfort following third molar surgery. more...
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- 2024
- Full Text
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48. Prostaglandin E2 depolarises sensory axons in vitro in an ANO1 and Nav1.8 dependent manner.
- Author
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Kimourtzis, Georgios, Rangwani, Natasha, Jenkins, Bethan J., Jani, Siddharth, McNaughton, Peter A., and Raouf, Ramin
- Subjects
- *
DORSAL root ganglia , *ACTION potentials , *CHLORIDE channels , *SODIUM channel blockers , *AXONS , *SODIUM channels - Abstract
Prostaglandin E2 (PGE2) is a major contributor to inflammatory pain hyperalgesia, however, the extent to which it modulates the activity of nociceptive axons is incompletely understood. We developed and characterized a microfluidic cell culture model to investigate sensitisation of the axons of dorsal root ganglia neurons. We show that application of PGE2 to fluidically isolated axons leads to sensitisation of their responses to depolarising stimuli. Interestingly the application of PGE2 to the DRG axons elicited a direct and persistent spiking activity propagated to the soma. Both the persistent activity and the membrane depolarisation in the axons are abolished by the EP4 receptor inhibitor and a blocker of cAMP synthesis. Further investigated into the mechanisms of the spiking activity showed that the PGE2 evoked depolarisation was inhibited by Nav1.8 sodium channel blockers but was refractory to the application of TTX or zatebradine. Interestingly, the depolarisation of axons was blocked by blocking ANO1 channels with T16Ainh-A01. We further show that PGE2-elicited axonal responses are altered by the changes in chloride gradient within the axons following treatment with bumetanide a Na-K-2Cl cotransporter NKCC1 inhibitor, but not by VU01240551 an inhibitor of potassium-chloride transporter KCC2. Our data demonstrate a novel role for PGE2/EP4/cAMP pathway which culminates in a sustained depolarisation of sensory axons mediated by a chloride current through ANO1 channels. Therefore, using a microfluidic culture model, we provide evidence for a potential dual function of PGE2 in inflammatory pain: it sensitises depolarisation-evoked responses in nociceptive axons and directly triggers action potentials by activating ANO1 and Nav1.8 channels. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
- View/download PDF
49. Determination of Prostaglandin E2 in Pork and Lymph Nodes by Ultra-Performance Liquid Chromatogrpahy-tandem Mass Spectrometry.
- Author
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WANG Wei, WU Wanqin, JIANG Feng, ZHU Xiaoling, and ZHANG Li
- Subjects
LIQUID chromatography-mass spectrometry ,LYMPH nodes ,PROSTAGLANDINS ,MASS spectrometry ,MASS transfer coefficients ,SOLID phase extraction - Abstract
A method was developed for the determination of prostaglandin E
2 in pork and lymph nodes based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Samples were extracted with acetonitrile, defatted with acetonitrile-saturated n-hexane, cleaned up by HLB solid-phase extraction columns, and the eluates were blown to near-dryness with nitrogen at 45 °C and determined by re-solubilizing in a 50% acetonitrile solution containing 0.2% formic acid. The separation was conducted on a C18 column with 0.1% formic acid solution and acetonitrile as mobile phases, and the multiple reaction monitoring was performed in negative ion mode. The limit of detection for prostaglandin E2 in pork and its products was 10 µg/kg, and the limit of quantification was 20 µg/kg. The recoveries of prostaglandin E2 in the method were in the range of 90~120%, and the precision was below 15.0%. The accuracy and precision of the method met the requirements for quantitative analysis. The values of prostaglandin E2 in non-lymph node samples were below the limit of quantification using the established method, and the range of prostaglandin E2 in lymph node samples was 20.7~101.0 µg/kg. By determining the amount of prostaglandin E2 in a sample, it can be used as an aid in identifying lymph nodes. This method is highly accurate and generalizable, and it provides strong technical support for combating the illegal use of lymph nodes. [ABSTRACT FROM AUTHOR] more...- Published
- 2024
- Full Text
- View/download PDF
50. Magnesium malate-modified calcium phosphate bone cement promotes the repair of vertebral bone defects in minipigs via regulating CGRP.
- Author
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Xu, Hailiang, Tian, Fang, Liu, Youjun, Liu, Renfeng, Li, Hui, Gao, Xinlin, Ju, Cheng, Lu, Botao, Wu, Weidong, Wang, Zhiyuan, Zhu, Lei, Hao, Dingjun, and Jia, Shuaijun
- Subjects
- *
BONE regeneration , *CALCIUM phosphate , *BONE cements , *MAGNESIUM , *CALCITONIN gene-related peptide , *RUNX proteins , *KIDNEYS , *HEART - Abstract
Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
- View/download PDF
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