Prostaglandins & other lipid mediators最新文献

{"title":"The effect of highly bioavailable forms of curcumin on lipoprotein(a) plasma levels: A systematic review and meta-analysis of randomized clinical studies","authors":"Federica Fogacci ,&nbsp;Ashot Avagimyan ,&nbsp;Arturo Cesaro ,&nbsp;Marco Bernardi ,&nbsp;Francesco Perone ,&nbsp;Marina Giovannini ,&nbsp;Arrigo Francesco Giuseppe Cicero","doi":"10.1016/j.prostaglandins.2025.106994","DOIUrl":"10.1016/j.prostaglandins.2025.106994","url":null,"abstract":"<div><div>Curcumin is a bioactive compound derived from the rhizome of <em>Curcuma longa</em> (turmeric) that has garnered increasing attention for its potential health benefits. However, its use in clinical practice is limited due to its generally poor bioavailability. This issue can be overcome using novel delivery systems that enhance curcumin’s solubility, extend its residence time in plasma, improve its pharmacokinetic profile, and increase its cellular uptake. Novel curcumin formulations with improved bioavailability have been suggested to elevate plasma concentrations of lipoprotein(a) (Lp(a)), but there is no definitive evidence of a causal relationship. To address this, a systematic literature search was conducted in multiple electronic databases to identify relevant randomized placebo-controlled clinical studies published without a time limit. A meta-analysis of data suggested that dietary supplementation with highly bioavailable forms of curcumin significantly reduces Lp(a) levels [Standardized Mean Difference (SMD)= -0.96 (95 % Confidence Interval (CI): −1.82, −0.11)]. The effect size was robust in the leave-one-out sensitivity analysis and was not primarily driven by any single study. Of course, the clinical significance of this observation should be more thoroughly evaluated in longer-term trials, where the combined metabolic and anti-inflammatory effects of curcumin have vascular protective effects.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"178 ","pages":"Article 106994"},"PeriodicalIF":2.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848655","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":"Oxysterols, age-related-diseases and nutritherapy: Focus on 7-ketocholesterol and 7β-hydroxycholesterol","authors":"Anne Vejux ,&nbsp;Imen Ghzaiel ,&nbsp;John J. Mackrill ,&nbsp;Irundika H.K. Dias ,&nbsp;Leila Rezig ,&nbsp;Mohamed Ksila ,&nbsp;Amira Zarrouk ,&nbsp;Thomas Nury ,&nbsp;Fatiha Brahmi ,&nbsp;Adil El Midaoui ,&nbsp;Smail Meziane ,&nbsp;Atanas G. Atanasov ,&nbsp;Sonia Hammami ,&nbsp;Norbert Latruffe ,&nbsp;Pierre Jouanny ,&nbsp;Gérard Lizard","doi":"10.1016/j.prostaglandins.2025.106993","DOIUrl":"10.1016/j.prostaglandins.2025.106993","url":null,"abstract":"<div><div>Age-related diseases are often associated with a disruption of RedOx balance that can lead to lipid peroxidation with the formation of oxysterols, especially those oxidized on carbon-7: 7-ketocholesterol (also known as 7-oxo-cholesterol) and 7β-hydroxycholesterol. Like cholesterol, these oxysterols have 27 carbons, they are composed of a sterane nucleus and have a hydroxyl function in position 3. The oxysterols 7-ketocholesterol and 7β-hydroxycholesterol are mainly formed by cholesterol autoxidation and are biomarkers of oxidative stress. These two oxysterols are frequently found at increased levels in the biological fluids (plasma, cerebrospinal fluid), tissues and/or organs (arterial wall, retina, brain) of patients with age-related diseases, especially cardiovascular diseases, neurodegenerative diseases (mainly Alzheimer’s disease), ocular diseases (cataract, age-related macular degeneration), and sarcopenia. Depending on the cell type considered, 7-ketocholesterol and 7β-hydroxycholesterol induce either caspase- dependent or -independent types of cell death associated with mitochondrial and peroxisomal dysfunctions, autophagy and oxidative stress. The caspase dependent type of cell death associated with oxidative stress and autophagy is defined as oxiapoptophagy. These two oxysterols are also inducers of inflammation. These biological features associated with the toxicity of 7-ketocholesterol, and 7β-hydroxycholesterol are often observed in patients with age-related diseases, suggesting an involvement of these oxysterols in the pathophysiology of these disorders. The cytotoxic effects of 7-ketocholesterol and 7β-hydroxycholesterol are counteracted on different cell models by representative nutrients of the Mediterranean diet: ω3 and ω9 fatty acids, polyphenols, and tocopherols. There are also evidences, mainly in cardiovascular diseases, of the benefits of α-tocopherol and phenolic compounds. These <em>in vitro</em> and <em>in vivo</em> observations on 7-ketocholesterol and 7β-hydroxycholesterol, which are frequently increased in age-related diseases, reinforce the interest of nutritherapeutic treatments to prevent and/or cure age-related diseases currently without effective therapies.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"178 ","pages":"Article 106993"},"PeriodicalIF":2.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855233","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":"An updated systematic review and meta-analysis of pomegranate consumption on lipid profile","authors":"Wengong Cheng ,&nbsp;Kaiqin Liang ,&nbsp;Aiqiong Huang","doi":"10.1016/j.prostaglandins.2025.106992","DOIUrl":"10.1016/j.prostaglandins.2025.106992","url":null,"abstract":"<div><div>Pomegranate, rich in bioactive compounds such as polyphenols and flavonoids, has been studied for its potential lipid-modulating effects, yet evidence remains inconsistent. This systematic review and meta-analysis aimed to evaluate the impact of pomegranate consumption on plasma lipid profiles by synthesizing data from randomized controlled trials (RCTs). Following PRISMA guidelines, 37 RCTs (n = 2695 participants) were included after searching Scopus and MEDLINE databases. Studies assessed pomegranate products (juice, extract, seed oil) administered orally for ≥ 7 days, with lipid parameters, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) as outcomes. Data were pooled using RevMan 5.3 with random-effects models. Results indicated that pomegranate intake significantly increased HDL-C levels (mean difference: 2.50 mg/dL, 95 % CI: 1.00–4.00, <em>p</em> &lt; 0.05), while no significant changes were observed in TC, LDL-C, or TG. Subgroup analyses revealed pronounced HDL-C elevation in non-alcoholic fatty liver disease (NAFLD) patients, health participants and interventions lasting ≥ 8 weeks. Heterogeneity across studies was attributed to variations in intervention duration, dosage forms, and participant characteristics. Publication bias was nonsignificant (Egger’s test, <em>p</em> &gt; 0.05). These findings suggest that pomegranate supplementation may improve HDL-C, potentially through modulation of HDL-associated enzymes like paraoxonase. However, further large-scale, long-term RCTs are warranted to confirm these effects and explore synergistic benefits with standard lipid-lowering therapies.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"178 ","pages":"Article 106992"},"PeriodicalIF":2.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842911","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":"Effects of walnut consumption on biomarkers of oxidative stress: A systematic review and meta-analysis of randomized controlled trials","authors":"Vali Musazadeh ,&nbsp;Mahsa Mahmoudinezhad ,&nbsp;Niloofar Hamidi ,&nbsp;Maryam Falahatzadeh ,&nbsp;Farzad Shidfar","doi":"10.1016/j.prostaglandins.2025.106986","DOIUrl":"10.1016/j.prostaglandins.2025.106986","url":null,"abstract":"<div><div>Oxidative stress is caused by an imbalance between accumulation and production of oxygen reactive species (ROS) in tissues and cells and play a key role in many diseases. This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to analyze the effects of walnut consumption on biomarkers of oxidative stress. Databases including PubMed, Scopus, Embase and Web of science were searched until November 30th, 2024. Data were subjected to meta-analysis using a random effects model to examine the effect sizes of the pooled results. Four studies were identified eligible to be included in current meta-analysis. Walnut consumption resulted in a significant increase in catalase activity (CAT) (WMD: 42.20; 95 % CI: 34.28, 50.11). Walnut consumption did not affect other biomarkers of oxidative stress such as lipid peroxidation (LPO), reduced glutathione (GSH), oxidized glutathione (GSSG) and oxygen radical absorbance capacity (ORAC). Overall, this meta-analysis demonstrated walnut consumption increase CAT, but did not affect other biomarkers of oxidative stress. This suggests that walnut may have played an indirect and mild role in health. However, due to the limited number of studies, further investigations is suggested in this regard.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"178 ","pages":"Article 106986"},"PeriodicalIF":2.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768314","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":"GLP-1RAs regulate lipid metabolism and induce autophagy through AMPK/SIRT1 pathway to improve NAFLD","authors":"Qiang Zhang ,&nbsp;Jingyuan Wang ,&nbsp;Xiaojin Hu ,&nbsp;Wei Lu ,&nbsp;Yang Cao ,&nbsp;Chunyan Niu ,&nbsp;Hongqin Yue","doi":"10.1016/j.prostaglandins.2025.106987","DOIUrl":"10.1016/j.prostaglandins.2025.106987","url":null,"abstract":"<div><h3>Background</h3><div>Non-alcoholic fatty liver disease (NAFLD) is a leading cause of cirrhosis and a major risk factor for hepatocellular carcinoma and liver-related death. Diabetes medications have been studied as potential treatments for NAFLD. Glucagon-like peptide-1 agonists (GLP-1RAs) have been rarely reported in the treatment of NAFLD alone as an anti-diabetic drug, and its specific mechanism of action is unknown. We investigated whether the therapeutic effect of liraglutide (LRG, a representative drug of GLP-1RAs) on hepatic steatosis is related to regulating lipid metabolism and enhancing autophagy in the hepatocytes.</div></div><div><h3>Methods</h3><div>We examined the effect of LRG on fat accumulation in fatty hepatocytes, and discussed its effects on enzymes related to lipid metabolism and autophagy. Meanwhile, knockdown of SIRT1 in free fatty acids(FFA)-treated cells was used to detected the influence of LRG on lipid metabolism and autophagy by regulating of AMPK/SIRT1 signaling.</div></div><div><h3>Results</h3><div>Our findings showed that free fatty acids (FFA) induced hepatocyte steatosis, which was significantly reversed by LRG. Meanwhile, LRG significantly regulated the expression of hepatocyte lipogenesis and cytosolic lipolysis-related proteins (FAS, ACC1, ATGL, HSL, LAL). Furthermore, LRG enhanced FFA-induced suppression of autophagy and SIRT1 expression, reducing intracellular lipid accumulation. It is evident that LRG regulates lipid metabolism and induces autophagy in an (AMPK)-dependent manner. Moreover, SIRT1 knockdown inhibited the autophagy-inducing and lipid-lowering effects of LRG.</div></div><div><h3>Conclusion</h3><div>GLP-1RAs may lower hepatic steatosis by regulating lipid metabolism and enhancing autophagy in an AMPK/SIRT1-dependent manner, providing a new target for the treatment of NAFLD.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"178 ","pages":"Article 106987"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768313","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}

{"title":"Effects of statin use on blood pressure and other hypertension-related outcome indicators in hypertensive patients: A systematic review and meta-analysis","authors":"Zhaohan Chu ,&nbsp;Wei Yue ,&nbsp;Qingqing Mu ,&nbsp;Dong Xu ,&nbsp;Zexu Chang ,&nbsp;Mengke Liang ,&nbsp;Yixiao Geng ,&nbsp;Ping Ding","doi":"10.1016/j.prostaglandins.2025.106991","DOIUrl":"10.1016/j.prostaglandins.2025.106991","url":null,"abstract":"<div><h3>Aims</h3><div>This meta-analysis delved into the impact of statin therapy, both as a monotherapy and in conjunction with antihypertensive medications, on blood pressure levels and outcomes pertinent to hypertension.</div></div><div><h3>Methods</h3><div>We searched the PubMed, EMBASE, and Cochrane databases for studies published before October 1 2023. Studies designed as cohort studies or randomized controlled trials and investigating the effects of single use of statin or its combined use with other antihypertensive therapy were included. Authors extracted the data independently and differences were decided through discussion. Random-effects model was used to evaluate the merged outcomes. Due to the high heterogeneity of the HDL-C group, we performed subgroup analysis according to the type of statin. To assess the robustness and potential publication bias of our findings, we utilized sensitivity analysis, Egger’s test, and funnel plots.</div></div><div><h3>Results</h3><div>23 trials were included in this meta-analysis. The primary outcomes revealed that administering statins did not significantly impact the systolic pressure (SBP) of hypertensive patients (MD, −1.77; 95 % CI, −4.82–1.27). —The promoted effect of statin treatment on diastolic pressure (DBP) in hypertensive patients was found (MD, −1.87; 95 % CI, −3.72 –-0.01). The secondary outcomes revealed that the use of statins resulted in a significant reduction in low-density lipoprotein (LDL-C), while significantly increasing high-density lipoprotein (HDL-C) in hypertensive patients.</div></div><div><h3>Conclusion</h3><div>Statin use did not modulate SBP and DBP of patients with hypertension, but SBP was decreased in the rosuvastatin or pravastatin subgroup, while DBP was decreased in the simvastatin or pravastatin subgroup. Statin treatment reduced LDL-C, increased HDL-C, and reduced the incidence of cardiovascular events and mortality compared to control groups.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"178 ","pages":"Article 106991"},"PeriodicalIF":2.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773212","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":"Decreased plasma lipoxin A4, resolvin D1, protectin D1 are correlated with the complexity and prognosis of coronary heart disease: A retrospective cohort study","authors":"Yun-fei Wang ,&nbsp;Xue-tao Zhu ,&nbsp;Ze-ping Hu","doi":"10.1016/j.prostaglandins.2025.106990","DOIUrl":"10.1016/j.prostaglandins.2025.106990","url":null,"abstract":"<div><div>This study aimed to assess the predictive capacity of specialized pro-resolving mediators (SPMs) regarding the complexity and prognosis of coronary heart disease (CHD). Total of 602 CHD patients were included in this study and categorized into low-risk, medium-risk, and high-risk groups based on the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score. Follow-up was conducted for two years, during which patients were dichotomized into poor and good prognosis groups. Additionally, twenty healthy controls were incorporated. Plasma concentrations of lipoxin A4 (LXA4), resolvin D1 (RvD1), protectin D1 (PD1), C-reactive protein (CRP), interleukin-6 (IL-6), and IL-10 were quantified. Plasma LXA4, RvD1, PD1, and the ratios LXA4/IL-6, RvD1/IL-6, PD1/IL-6 exhibited a gradual decrease across control, low-risk, medium-risk, and high-risk groups and exhibited a negative correlation with the SYNTAX score. Spearman’s correlation analysis revealed negative correlations between plasma LXA4, RvD1, PD1, and both CRP and IL-6, and positive correlations with IL-10. Multiple linear regression models demonstrated negative associations between plasma LXA4, RvD1, PD1, and SYNTAX score. Moreover, both univariate and multivariate binary logistic regression analyses identified plasma LXA4, RvD1, and PD1 as protective factors against medium/high-risk SYNTAX score categorization. In the poor prognosis group, plasma PD1 was reduced at short-term follow-up, and the ratios LXA4/IL-6, RvD1/IL-6, PD1/IL-6 were reduced at long-term follow-up. Plasma LXA4, RvD1, and PD1 demonstrated negative correlations with CHD complexity and potentially served as protective factors against CHD. Plasma PD1 provided predictive value for short-term prognosis, while the ratios LXA4/IL-6, RvD1/IL-6, PD1/IL-6 were indicative for long-term prognosis.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"178 ","pages":"Article 106990"},"PeriodicalIF":2.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753824","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":"E2F7 upregulates MCM4 and fatty acid metabolism to advance lung adenocarcinoma metastasis","authors":"WuAsen Tang ,&nbsp;Deming Zhang ,&nbsp;Di Liu,&nbsp;Zikang Liu,&nbsp;Kuang Xiao,&nbsp;Chenggang Lei,&nbsp;Yalun Yang,&nbsp;Qian Zhou,&nbsp;Xianghui Wang","doi":"10.1016/j.prostaglandins.2025.106988","DOIUrl":"10.1016/j.prostaglandins.2025.106988","url":null,"abstract":"<div><h3>Background</h3><div>MCM4, a key protein in MCM, is frequently overexpressed in cancers, but its specific role in lung adenocarcinoma (LUAD) metastasis is unclear.</div></div><div><h3>Methods</h3><div>Bioinformatics revealed the mRNA expression pattern of MCM4 in LUAD, which we confirmed in both normal lung epithelial and adenocarcinoma cell lines using qRT-PCR and western blot (WB). Cellular proliferation was gauged by cell counting kit-8 and colony formation assays, and the expression of epithelial-mesenchymal transition markers along with fatty acid synthase (FASN) was probed via WB. We employed Transwell to assess cellular migration and invasion, and utilized kits for quantifying intracellular triglycerides and phospholipids. Bioinformatics identified E2F7 as a potential transcriptional regulator of MCM4, prompting us to explore its relationship with MCM4, including predicted binding sites and E2F7 mRNA expression in LUAD. Chromatin immunoprecipitation and dual-luciferase reporter assays were conducted to validate the regulatory effects of E2F7 on MCM4.</div></div><div><h3>Results</h3><div>MCM4 was found to be overexpressed in LUAD, and its knockdown inhibited cancer cell proliferation, migration, invasion, and metastasis, along with decreased FASN expression and declined levels of triglycerides and phospholipids within cells. Mechanistically, E2F7 transcriptionally activated MCM4, regulating fatty acid metabolism and promoting LUAD progression and metastasis.</div></div><div><h3>Conclusion</h3><div>Our study elucidates the mechanism by which E2F7 transcriptionally controls MCM4 to activate fatty acid metabolism, fueling LUAD metastasis. These discoveries emphasize the pivotal function of lipid metabolism in LUAD development and suggests new therapeutic targets for LUAD treatment.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"178 ","pages":"Article 106988"},"PeriodicalIF":2.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753913","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":"Suppression of adipose TGF-β1 by probiotics alleviates metabolic disturbance in experimentally induced PCOS","authors":"Kehinde S. Olaniyi ,&nbsp;Doris O. Okara,&nbsp;Stephanie E. Areloegbe","doi":"10.1016/j.prostaglandins.2025.106989","DOIUrl":"10.1016/j.prostaglandins.2025.106989","url":null,"abstract":"<div><h3>Background</h3><div>Polycystic ovarian syndrome (PCOS) is critically characterized with metabolic and endocrine dysfunctions, precipitating metabolic syndrome and infertility in reproductive aged women. Adipose tissue dysfunction has been implicated in the pathogenesis of metabolic syndrome, including in PCOS individuals. Probiotics are healthy bacteria in the gut that regulate metabolic health. However, the impact of probiotics on adipose-driven metabolic syndrome has not been reported. The present study therefore hypothesized that probiotics would attenuates metabolic disturbance in experimental PCOS rat model, probably by suppression of TGF-β1.</div></div><div><h3>Materials and methods</h3><div>Eight-week-old female Wistar rats were randomly allotted into four groups (n = 5). Administration of letrozole (1 mg/kg <em>p.o</em>) for 21 days induced PCOS, thereafter the animals were treated with 3x10⁹ CFU (<em>p. o</em>) of probiotics for six weeks.</div></div><div><h3>Results</h3><div>Letrozole-induced PCOS rats were characterized with elevated circulating testosterone, and multiple ovarian cysts. In addition, rats with PCOS developed increased body weight, which was also accompanied with insulin resistance, hyperinsulinemia, and increased leptin, and decreased adiponectin and adipose TG, as well as elevated adipose lipase. Inflammatory markers (NF-kB, TNF-α) were elevated, while antioxidant defense (GSH) was depleted in PCOS animals. A significant increase in adipose TGF-β1, caspase-6 and HDAC2 levels was observed in PCOS rats when compared with the control. Immunohistochemical evaluation of adipose tissue also showed severe expression of NLRP3 in PCOS rats and these changes were accompanied by increased level of TGF-β1. However, treatment with probiotics reversed these aberrant systemic and adipose tissue changes in PCOS model.</div></div><div><h3>Conclusion</h3><div>The present results suggest the therapeutic benefit of probiotics against metabolic disturbance in PCOS model through suppression of TGF-β1-dependent pathway.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"178 ","pages":"Article 106989"},"PeriodicalIF":2.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143716315","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":"Ceramide and DNA damage in liver fibrosis: Exploring the implications of eicosapentaenoic acid encapsulation in cellulose nanocrystals","authors":"Jihan Hussein ,&nbsp;Mona A. El-Bana ,&nbsp;Rehab A. Mohamed ,&nbsp;Enayat Omara ,&nbsp;Dalia Medhat","doi":"10.1016/j.prostaglandins.2025.106985","DOIUrl":"10.1016/j.prostaglandins.2025.106985","url":null,"abstract":"<div><div>Ceramide plays a crucial role in promoting liver fibrosis by inducing apoptosis and inflammation in hepatocytes. Oxidative stress accelerates fibrosis by elevating levels of urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), an indicator for the damage of DNA. We aimed to evaluate the efficacy of eicosapentaenoic acid encapsulated in cellulose nanocrystals (EPA-CNC) in inhibiting ceramide accumulation and reducing urinary 8-OHdG levels, thus providing protective effects against the progression of liver fibrosis.</div><div>In this study, twenty-four adult male Wistar albino rats were allocated into a negative control group, a group with liver fibrosis induced by diethylnitrosamine (DEN), and a group with DEN-induced liver fibrosis treated simultaneously with EPA-CNC. Key parameters assessed included liver paraoxonase-1 (PON-1), plasma interleukin-6 (IL-6), plasma ceramide, liver hydroxyproline (Hyp) content, and urinary 8-OHdG.</div><div>DEN-induced liver fibrosis led to a significant increase in inflammatory markers, including ceramide, IL-6, and notably urinary 8-OHdG. This was accompanied by a decrease in PON-1 activity and increased collagen deposition in liver tissues (Hyp content). Histopathological analysis revealed a substantial loss of liver architecture, with inflammation and fibrosis surrounding necrotic areas.</div><div>In contrast, treatment with encapsulated EPA-CNC resulted in a significant decrease in plasma ceramide, IL-6, liver Hyp content, and urinary 8-OHdG levels, along with an improvement in liver PON-1 activity. Histopathological findings showed nearly normal liver architecture.</div><div>In conclusion, increased levels of ceramide and urinary 8-OHdG could serve as indicators of ongoing hepatocellular damage due to their positive correlations with fibrotic markers. Encapsulated EPA-CNC may offer a promising approach for halting oxidative stress and inflammation in liver fibrosis.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"178 ","pages":"Article 106985"},"PeriodicalIF":2.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674616","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}