Prostaglandins & other lipid mediators最新文献

{"title":"Effect of curcumin on lipid mediators, glycemic index, and oxidative stress and inflammation biomarkers in polycystic ovary syndrome: Future directions and current knowledge – A systematic review","authors":"Hiba Muwafaq Saleem ,&nbsp;Hussein Riyadh Abdul Kareem Al-Hetty ,&nbsp;Abdulrahman T. Ahmed ,&nbsp;Muthanna M. Awad ,&nbsp;Mohammed Qais Al-Ani ,&nbsp;Mustafa Nuhad Al-Darraji ,&nbsp;Dina Akeel Salman ,&nbsp;Loay H. Ali","doi":"10.1016/j.prostaglandins.2024.106947","DOIUrl":"10.1016/j.prostaglandins.2024.106947","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is one of the most common and important polygenic endocrine disorders among women of reproductive-aged. Current treatments are mostly used only to control the signs and symptoms of the disease, while not being able to completely prevent complications. Curcumin is one of the active compounds in turmeric, which is commonly used for a wide range of metabolic and inflammatory diseases. Therefore, this systematic review was performed to evaluate the effect of curcumin supplementation on PCOS. The current systematic review was performed according to the guidelines of the 2015 PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statements. We searched ProQuest, PubMed, Google Scholar electronic, Scopus, and Cochrane, Embase, and Science Direct databases and on articles published up until November 2024. All of the animal studies (seven studies) and clinical trials (five studies) included in this systematic review that assessed the effect of curcumin on, reproductive hormones and metabolic risk markers in PCOS were published in English-language journals. Most studies supported the beneficial effects of curcumin on folliculogenesis, ovarian histomorphology, and luteinization processes. The effects of curcumin on decreasing the levels of luteinizing insulin resistance luteinizing hormone (LH), Follicle-stimulating hormone (FSH)and testosterone, were also reported. Curcumin also improved dyslipidemia, but no significant effect on weight loss has been reported. It is suggested that the effect of curcumin in PCOS is more related to the antioxidant and anti-inflammatory properties of curcumin than to the effects of weight loss. Therefore, this study provides evidence that curcumin can be considered an effective factor in reducing the complications of PCOS. However, due to the low number of human studies in this field, further clinical trials are warranted to verify these outcomes.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"177 ","pages":"Article 106947"},"PeriodicalIF":2.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cigarette smoke-induced attenuation of the prostaglandin transporter SLCO2A1 expression through aryl hydrocarbon receptor","authors":"Melody N. Shumba,&nbsp;Yoshinobu Nakamura,&nbsp;Takeo Nakanishi","doi":"10.1016/j.prostaglandins.2024.106935","DOIUrl":"10.1016/j.prostaglandins.2024.106935","url":null,"abstract":"<div><div>SLCO2A1 is a prostaglandin transporter and contributes to regulating local concentration of an inflammatory mediator, PGE₂. Since we previously found that cigarette smoke extracts (CSE) reduced Slco2a1 mRNA expression in rat alveolar epithelial cells, the current study aimed to investigate the effect of CSE on human SLCO2A1 mRNA expression across cell lines from organs that are susceptible to tobacco smoking-induced inflammation. 5’-Flanking regions of SLCO2A1 up to 3673 bp upstream of the transcription start site (+1) was sub-cloned into a luciferase (LUC) expression vector, and promoter activity was evaluated by a reporter assay. CSE significantly reduced SLCO2A1 mRNA expression and LUC activity driven by the construct of −3673/+4 in colon epithelial LoVo and Caco-2 and lung mucoepidermoid NCI-H292 cells, but not in liver epithelial-like HepG2 cells. Long-term exposure of LoVo cells to CSE completely suppressed SLCO2A1 protein expression. The CSE-mediated effect on LUC activity was restored by an AHR antagonist PD98059 and a known AHR ligand β-naphthoflavone significantly reduced SLCO2A1 mRNA expression in cells. Concomitantly, the CSE-mediated negative regulation of SLCO2A1 was abolished in cells transfected with the construct of −3673/+4 with mutated xenobiotic response element. Furthermore, PD98059 and an AHR inhibitor perillaldehyde diminished the negative effect of CSE on SLCO2A1 mRNA expression in Lovo, NCI-H292 and Caco-2 cells. These results demonstrate that CSE negatively modulates SLCO2A1 transcription through AHR activation, providing a toxicological implication of tobacco smoke-induced inflammation.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"176 ","pages":"Article 106935"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective role of Yougui Yin in experimental knee osteoarthritis: From the perspective of macrophage polarization","authors":"Zhongqing Wu ,&nbsp;Kanna Xu ,&nbsp;Minchang Chen ,&nbsp;Shihao Wang ,&nbsp;Yong Ma","doi":"10.1016/j.prostaglandins.2024.106940","DOIUrl":"10.1016/j.prostaglandins.2024.106940","url":null,"abstract":"<div><div>Knee osteoarthritis (KOA) refers to a prevalent musculoskeletal disorder, frequently complicated by substantial pain and physical disability. Yougui Yin (YGY) is a classic Chinese herbal mixture which has demonstrated potential in treating KOA. Considering that, its cryptic mechanism warrants to be deciphered, which is the subject of our present research. In vivo, H&amp;E staining, Alcian blue staining and Masson staining assessed the histomorphology. Commercial kits and ELISA evaluated oxidative stress markers. ELISA also assayed serum inflammatory cytokines. TUNEL staining appraised apoptosis. Western blotting examined cartilage matrix degradation, apoptotic and NLRP3 inflammasome proteins. Immunofluorescence assay estimated macrophage polarization. In vitro, ELISA assayed oxidative stress markers and inflammatory cytokines. Immunofluorescence and flow cytometry assay estimated macrophage polarization. MTT and flow cytometry assays severally measured cell viability and apoptosis. DCFH-DA probe detected ROS formation. RT-qPCR and Western blotting examined chondrocyte markers, apoptotic and pyroptotic genes. YGY significantly eased the histomorphological damage, apoptosis and pyroptosis in the cartilage tissues of KOA mice. Besides, YGY exerted anti-oxidant and anti-inflammatory activities and drove M1-to-M2 polarization of macrophages both in vitro and in vivo. Further, the co-culture of macrophages treated by LPS and serum containing YGY improved the viability, eliminated the apoptosis, pyroptosis, inflammation, oxidative stress and cartilage degradation in TNF-α-exposed chondrocytes co-cultured with LPS-intervened macrophages. Overall, YGY might mediate macrophage polarization to impede the advancement of KOA.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"176 ","pages":"Article 106940"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alleviating effects of Nigella sativa supplements on biomarkers of inflammation and oxidative stress: Results from an umbrella meta-analysis","authors":"Xinyu Lan ,&nbsp;Yongliang Xia","doi":"10.1016/j.prostaglandins.2024.106945","DOIUrl":"10.1016/j.prostaglandins.2024.106945","url":null,"abstract":"<div><div>Several meta-analyses have examined the effect of <em>Nigella sativa (N. Sativa)</em> supplementation on inflammatory and oxidative markers, with conflicting results. So, the current study evaluated the effect of <em>N. Sativa</em> on some oxidative and inflammatory parameters. The Embase, Web of Science, Scopus, PubMed databases, and Google Scholar were systemically searched to identify papers indexed before February 2023. The pooled results were calculated with the use of a random-effects model to evaluate the effects of <em>N. Sativa</em> on inflammatory and oxidative markers. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of evidence. Overall, seven meta-analyses were included in the study. <em>N. Sativa</em> supplementation significantly decreased serum C-reactive protein (CRP) (ES = −0.42; 95 % CI: −0.58, −0.25, p &lt; 0.001), tumor necrosis factor-alpha (TNF-α) (ES= −1.27; 95 % CI: −2.29, −0.25; p = 0.015), and malondialdehyde (MDA) (ES = −0.67; 95 % CI: −0.97, −0.36, p &lt; 0.001) levels, and significantly improved total antioxidant capacity (TAC) (ES = 0.34; 95 % CI: 0.20, 0.47, p &lt; 0.001) and superoxide dismutase (SOD) (ES = 50.66; 95 % CI: 34.15, 67.18, p &lt; 0.001) levels. <em>N. Sativa</em> supplementation had beneficial effects on CRP, TNF-α, MDA, SOD, and TAC. Thus, <em>N. Sativa</em> can be recommended as an adjuvant anti-inflammatory and anti-oxidant agent.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"176 ","pages":"Article 106945"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TFAP2A activates CTHRC1 to influence the migration of lung adenocarcinoma cells by modulating fatty acid metabolism","authors":"Xiaodong Zheng ,&nbsp;Junzheng Zhou ,&nbsp;Shiwei Nie ,&nbsp;Yuan Chen ,&nbsp;Xudong Wei ,&nbsp;Jinrui Zhang ,&nbsp;Xiaojuan Shen ,&nbsp;Weimin Zhang","doi":"10.1016/j.prostaglandins.2024.106941","DOIUrl":"10.1016/j.prostaglandins.2024.106941","url":null,"abstract":"<div><h3>Background</h3><div>Tumor metastasis is the main cause of death in lung adenocarcinoma (LAC) patients. It is known that the collagen triple helix repeats containing 1 (CTHRC1) protein is implicated in tissue remodeling and is tightly linked to the carcinogenesis and metastasis of solid tumors. However, the functional role of CTHRC1 and its potential mechanisms in LAC cell metastasis have not been fully explored.</div></div><div><h3>Methods</h3><div>The expression level of CTHRC1 in LAC was measured by using bioinformatics analysis combined with quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB). Small interfering RNA and overexpression methods were employed to investigate the function and molecular mechanisms of CTHRC1 in LAC cells. Through bioinformatics analysis, qRT-PCR, WB, scratch healing assay, Transwell, assay kits, and flow cytometry, the downstream pathways and upstream regulatory genes of CTHRC1 in LAC cells were investigated. The binding sites were verified by using chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene experiments.</div></div><div><h3>Results</h3><div>In this project, CTHRC1 was found to be abnormally upregulated in LAC tissues and cells. CTHRC1 promoted the migration and invasion of LAC cells. The promoting effect of CTHRC1 overexpression on LAC cell migration was weakened after the addition of orlistat (a fatty acid synthase inhibitor). Mechanistically, TF AP-2α (TFAP2A) was directly bound to the upstream sequence of the CTHRC1 promoter and promoted CTHRC1 expression. The TFAP2A-CTHRC1 axis induced the migration of LAC cells by activating fatty acid metabolism.</div></div><div><h3>Conclusion</h3><div>Our results indicated that TFAP2A activates fatty acid metabolism by positively modulating the expression of CTHRC1, thereby facilitating tumor cells’ migration and invasion. These findings provided novel insights into LAC treatment and future research.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"176 ","pages":"Article 106941"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory protein levels in asthmatic bronchitis: A study in the Duhok population, Iraq","authors":"Omar A.M. Al-Habib ,&nbsp;Hamdia Yousif Issa ,&nbsp;Taner Dastan ,&nbsp;Sevgi Durna Dastan ,&nbsp;Ali A. Ramadhan ,&nbsp;Zeliha Selamoglu","doi":"10.1016/j.prostaglandins.2024.106942","DOIUrl":"10.1016/j.prostaglandins.2024.106942","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aims to determine the levels of TNF-α, IGF-1, IL-6, and IL-10 protein in blood samples and their potential link to bronchitis-asthma diseases in the Iraq Duhok population, highlighting the prevalence of these long-term inflammatory diseases.</div></div><div><h3>Methods</h3><div>Sixty blood samples were used and separated into patients (n = 43) and control (n = 17) groups. Serum samples were separated for each individual. Elisa method was used in terms of 4 different proteins investigated in blood samples with the manufacturer’s instruction brand kits.</div></div><div><h3>Results</h3><div>This study evaluated TNF-α, IGF-1, IL-6, and IL-10 protein levels in blood samples from asthmatic bronchitis patients in Duhok. Although these levels were elevated compared to controls, the differences were not statistically significant.</div></div><div><h3>Conclusion</h3><div>The differences thought to be related to the bronchitis-asthma diseases could not be demonstrated between the patient and control groups in Iraq Duhok population. Future research should explore larger sample sizes and stratified patient groups to identify potential biomarkers.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"176 ","pages":"Article 106942"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative approaches to eczema treatment: A review of Fevipiprant and its potential as a new therapeutic agent","authors":"Rahul Jaiswal ,&nbsp;Sageer Ahmad ,&nbsp;Supriya Pandey ,&nbsp;Asad Ali ,&nbsp;Rupali Jaiswal ,&nbsp;Reetu Yadav ,&nbsp;Reema Yadav ,&nbsp;Rabiya Ahsan ,&nbsp;Tapasya Dwivedi","doi":"10.1016/j.prostaglandins.2024.106946","DOIUrl":"10.1016/j.prostaglandins.2024.106946","url":null,"abstract":"<div><div>Eczema is also known as atopic dermatitis, which goes on to affect the skin as a chronic inflammatory disease. It is associated with a constant feeling of scratchiness, erthyma and disruption of the natural skin barrier. Treatment provided at present may improve some of the symptoms, for instance use of corticosteroids or immunosuppressive agents, however, there is an overwhelming need for better focused and effective methods of treatment with minimal adverse effects. Fevipiprant, a DP2 receptor antagonist, has emerged as a promising agent targeting prostaglandin D2 (PGD2) pathways, which play a crucial role in eczema pathophysiology.</div><div>This review examines the mechanism of action, pharmacological profile of Fevipiprant and present studies on preclinical and clinical development of Fevipiprant for treatment of eczema. Additionally, we provide a comparison of Fevipiprant with existing treatment options and evaluate its safety and tolerability. The evaluation gives a reason that targeting in the treatment of eczema by the use of Fevipiprant is able to effectively target the DP2 pathway which is associated with a good safetyl however presenting itself as a new treatment option in the management of eczema. Finally, long-term studies are essential to validate the feasibility, safety, and effectiveness of Fevipiprant compared to existing therapies for eczema. Novartis has taken advantage of this stat for comp… given the scarcity of effective therapies for paediatric atopic dermatitis in Japan. Exploring Fevipiprant from the Efficacy Perspective is also required because it will impact how it will enter clinical practice in therapy of eczema in the future.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"176 ","pages":"Article 106946"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potassium channels mediate nitric oxide-induced vasorelaxation in arteries supplying colon cancer","authors":"Kamaran.H. Mohammed ,&nbsp;Sardar H. Arif ,&nbsp;Lina N. Adam ,&nbsp;Omar A.M. Al-Habib","doi":"10.1016/j.prostaglandins.2024.106937","DOIUrl":"10.1016/j.prostaglandins.2024.106937","url":null,"abstract":"<div><h3>Introduction</h3><div>Aberrant vascular function and cancer growth are closely related, with nitric oxide (NO) being a key factor in vascular tone regulation. This study provides Novel insights into the distinctive mechanisms underlying cancer-associated vascular dysfunction by investigating the involvement of potassium (K⁺) channels in NO-mediated vasorelaxation within arteries supplying colon cancer.</div></div><div><h3>Methods</h3><div>Arterial segments from colon cancer patients were isolated and sectioned into rings, these rings were mounted in an organ bath filled with Krebs' solution and maintained at 37°C. Isometric tension recordings were obtained using a force transducer connected to a PowerLab Data Acquisition System. Arterial segments were pre-incubated with a variety of K⁺ channel blockers, both individually and in combination, including glibenclamide (GLIB), barium chloride (BaCl₂), tetraethylammonium (TEA), and 4-aminopyridine (4-AP). Concentration-response curves were designed to evaluate how K⁺ channel blocking affected the vasodilation caused by NO.</div></div><div><h3>Results</h3><div>Sodium nitroprusside (SNP) induced vasorelaxation in arterial rings from colon cancer, influenced by specific K+ channels. Pre-incubation with TEA significantly reduced Emax to 60.22 ± 8.14 %, compared to 124.91 ± 15.07 % in controls, while GLIB decreased Emax to 113.10 ± 3.87 %. BaCl2 and 4-AP further diminished relaxation, and combined K⁺ channel blockers showed complex, non-additive effects. Distinct contributions of K_Ca and K_V channels to NO-induced vasodilation were elucidated. Additionally, interaction between NO and L-type calcium (Ca²⁺) channels suggested a novel vasorelaxation mechanism in cancerous tissues.</div></div><div><h3>Conclusion</h3><div>This research offers new perspectives on the intricate relationship between vascular biology and cancer development, emphasizing the promise of targeting potassium channels to address vascular abnormalities in cancer.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"176 ","pages":"Article 106937"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between omega-3 fatty acid-derived lipid mediators and markers of inflammation in older subjects with low-grade chronic inflammation","authors":"Stefania Lamon-Fava","doi":"10.1016/j.prostaglandins.2025.106948","DOIUrl":"10.1016/j.prostaglandins.2025.106948","url":null,"abstract":"<div><div>Cardiovascular disease (CVD), the leading cause of death in the United States and globally, is a chronic inflammatory disease likely caused by an impaired ability to resolve inflammation. Pre-clinical studies have provided strong evidence of the activating role of specialized pro-resolving lipid mediators (SPMs) derived from the omega-3 fatty acids eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) on the resolution of inflammation. However, there is a dearth of information on the role of SPMs on inflammation in humans. Therefore, the aim of this study was to assess whether plasma concentrations of omega-3 fatty acids and their derived SPMs are associated with inflammatory markers in subjects with low-grade chronic inflammation (C-reactive protein &gt;2 µg/mL). The plasma phospholipid content of omega-3 fatty acids, a marker of dietary intake, plasma concentrations of SPMs, and serum concentrations of inflammatory markers were measured in 21 older men and postmenopausal women (age 53–73 y) at the end of a four-week placebo phase (3 g/day high oleic acid sunflower oil). The phospholipid DHA content was inversely related to interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and IL-10 concentrations. Moreover, MCP-1 was inversely associated with the DHA-derived 14-HDHA and 4-HDHA, and IL-10 was inversely associated with EPA-derived 18-HEPE, 12-HEPE and 5-HEPE, DPA-derived Rv5_DPA, and DHA-derived 4-HDHA. These findings support the anti-inflammatory effect of dietary omega-3 fatty and suggest that lipid mediators derived from EPA, DPA, and DHA participate in the regulation of inflammation in subjects with chronic inflammation.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"176 ","pages":"Article 106948"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A high seizure burden increases brain concentrations of specialized pro-resolving mediators in the Scn1a+/- mouse model of Dravet syndrome","authors":"Ka Lai Yip ,&nbsp;Cilla Zhou ,&nbsp;Lyndsey L. Anderson ,&nbsp;Nicole A. Hawkins ,&nbsp;Jennifer A. Kearney ,&nbsp;Jonathon C. Arnold","doi":"10.1016/j.prostaglandins.2024.106943","DOIUrl":"10.1016/j.prostaglandins.2024.106943","url":null,"abstract":"<div><h3>Objective</h3><div>Dravet syndrome is a severe, intractable epilepsy in which 80 % of patients have a <em>de novo</em> mutation in the gene <em>SCN1A</em>. We recently reported that a high seizure burden increased hippocampal concentrations of an array of pro-inflammatory prostaglandins in the <em>Scn1a</em>^<em>+/-</em> mouse model of Dravet syndrome. This raised the possibility that a high seizure burden might also trigger the accumulation of specialized pro-resolving mediators that facilitate the resolution of neuroinflammation and brain repair. The present study therefore aimed to examine whether a high seizure burden increased hippocampal concentrations of various specialized pro-resolving mediators in the <em>Scn1a</em>^<em>+/-</em> mouse model of Dravet syndrome.</div></div><div><h3>Methods</h3><div><em>Scn1a</em>^<em>+/-</em> mice at postnatal day 21 (P21) were primed with a single hyperthermia-induced seizure event to induce a high seizure burden. On P24 primed <em>Scn1a</em>^<em>+/-</em> mice with a high seizure burden, unprimed naïve <em>Scn1a</em>^<em>+/-</em> mice and wild-type (WT) mice were euthanized and hippocampal tissue was collected for analysis of various specialized pro-resolving mediators using liquid chromatography mass spectrometry.</div></div><div><h3>Results</h3><div><em>Scn1a</em>^<em>+/-</em> mice with a high seizure burden showed increased hippocampal concentrations of the pro-inflammatory leukotrienes B4 and E4. Further, a high seizure burden increased hippocampal concentrations of various special pro-resolving mediators, including the maresins (maresin1), D-series resolvins (RVD1 and RVD4), and protectin (PCTR1). To further characterize these changes, we determined the mRNA expression of lipoxygenase genes, as these synthetic enzymes are common across classes of specialized pro-resolving mediators. However, hippocampal expression of <em>Alox5</em>, <em>Alox12</em> and <em>Alox15</em> were not influenced by a high seizure burden.</div></div><div><h3>Significance</h3><div>We report for the first time that a high seizure burden increases the hippocampal concentrations of various specialized pro-resolving mediators in <em>Scn1a</em>^<em>+/-</em> mice. This provides a platform for future studies to examine whether modulation of these mediators might be exploited to reduce seizures and facilitate brain repair in intractable epilepsy syndromes.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"176 ","pages":"Article 106943"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}