Search Results (146)

Background and Aims: Injectable lipid emulsions are an integral component of parenteral nutrition, providing energy as well as essential fatty acids. However, conventional soybean oil–based emulsions, which are rich in omega-6 fatty acids, are associated with a risk of exacerbating pro-inflammatory responses and immunosuppression, which is of particular importance in critically ill patients. The aim of this review is to present the significance of the composition of modern injectable lipid emulsions, with particular emphasis on emulsions containing fish oil as a source of omega-3 fatty acids (EPA and DHA), and to discuss their potential clinical benefits in selected critical conditions. Methods: This narrative review discusses the rationale for modern mixed-oil ILE, with a focus on fish oil as a source of EPA and DHA, and summarizes potential clinical benefits in selected critical care settings. Results: Modern injectable lipid emulsions combine long-chain triglycerides derived from soybean oil (omega-6), MCTs, olive oil (omega-9), and fish oil (omega-3). Adjusting the supply of individual fractions affects cell membrane structure, signaling pathways, gene expression, and the profile of lipid mediators produced, including specialized pro-resolving mediators (SPMs). ESPEN guidelines and international recommendations emphasize the need to use lipids in parenteral nutrition, preferring mixed-oil ILE supplemented with fish oil. The cited meta-analyses and clinical studies indicate that omega-3-containing emulsions may reduce the risk of infections and sepsis; shorten hospital stay, ICU length of stay, and duration of mechanical ventilation in patients with sepsis; as well as improve outcomes in acute pancreatitis; lower the risk of delirium; and reduce the incidence of delayed gastric emptying. Conclusions: Available data support the use of mixed-oil ILE supplemented with fish oil in the parenteral nutrition of critically ill patients as a strategy with immunomodulatory and pro-resolving potential that may translate into improved clinical outcomes. However, further well-designed randomized trials are needed to optimize dosing and administration regimens. Full article

Sepsis-induced liver injury (SILI) stands as an independent prognostic factor for mortality among patients diagnosed with sepsis. Maresin-1 (MaR1) is a proresolving lipid mediator. However, its significance in SILI is uncertain. The current study sought to investigate MaR1’s effectiveness in treating SILI, as well as its molecular mechanism. In male C57BL/6J mice, we generated a SILI model by using cecal ligation and puncture (CLP). We further investigated how MaR1 influences inflammation, hepatic autophagy and apoptosis. We showed that treatment with MaR1 ameliorates SILI-induced hepatic injury, as reflected in decreased blood level of the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes, as well as better appearance of liver tissues. Furthermore, this medication markedly reduced the expression of inflammatory mediators. Importantly, MaR1 inhibited hepatocyte apoptosis by regulating the Bax/Bcl-2 ratio, decreasing cleaved caspase-3 expression, lowering apoptotic cell count, and increasing autophagy. The findings demonstrated that MaR1 treatment reduced p62 protein expression while raising Beclin1 levels and the LC3-II/LC3-I ratio, and facilitated autophagosome formation. The observed effects were most likely due to the stimulation of PI3K/Akt signaling, which was completely prevented by LY294002 (LY), a specific PI3K inhibitor. MaR1’s protective effect in SILI may be mediated via stimulation of the PI3K/Akt pathway, which reduces inflammation and regulates apoptosis and autophagy. Our results give additional experimental evidence of the potential therapeutic uses of MaR1 in the treatment of SILI. Full article

Chronic kidney disease (CKD) affects more than 10% of the population and is associated with a persistent, low-grade inflammatory state that accelerates tubulointerstitial fibrosis, worsens prognosis, and increases cardiovascular risk. This review aims to synthesize current knowledge on specialized pro-resolving mediators (SPMs) in the context of CKD pathophysiology, biomarkers, and therapeutic potential. We discuss key anti-inflammatory and pro-resolving mechanisms of SPMs that translate into nephroprotective and antifibrotic effects in experimental kidney models. The review summarizes data on EPA/DHA supplementation, including its impact on lipid profiles, inflammatory biomarkers (CRP, IL-6, TNF-α), and oxidative stress in patients with CKD. We also highlight contemporary analytical methods for biomarker assessment (LC-MS/MS, UHPLC-HRMS) and their potential for monitoring inflammatory activity across its phases (initiation, attenuation, resolution), CKD progression, and responses to ω-3/SPM-based interventions. Finally, we discuss the therapeutic potential of SPMs, as well as safety considerations and pharmacological interactions. In conclusion, SPMs and ω-3-derived mediators represent promising research and clinical targets as markers and modulators of inflammation in CKD, but require further validation in well-designed prospective studies. Full article

Aging is accompanied by profound alterations in immune function that collectively drive increased susceptibility to infection, reduced vaccine efficacy, impaired tissue repair, and heightened risk of age-related diseases (ARDs). These alterations are characterized by the coexistence of immunosenescence and inflammaging. Rather than reflecting isolated cellular defects, immune aging emerges as a systems-level reprogramming of immune networks that disrupts the initiation, resolution, and regenerative phases of inflammatory responses. In particular, aging is associated with impaired resolution of inflammation, defective efferocytosis, reduced responsiveness to pro-resolving signals, and diminished regenerative capacity, leading to persistent inflammatory milieus and tissue damage. This review summarizes recent advances in the mechanisms underlying immune dysfunction in aging, with a focus on how chronic inflammation, failed resolution, and defective repair reinforce one another. We discuss how alterations in innate and adaptive immunity, immunometabolism, cellular senescence, and immune–tissue interactions drive inflammaging and contribute to major ARDs, including cancer, neurodegenerative, and cardiometabolic diseases. Finally, we highlight emerging therapeutic strategies aimed at restoring immune balance and resolution. By adopting a systems-level and network-based perspective, this review underscores immune aging as a modifiable driver of ARDs and identifies key knowledge gaps and future directions toward interventions that promote healthy aging and extended healthspan. Full article

Background/Objectives: The retina is enriched in polyunsaturated fatty acids (PUFAs) which are indispensable for normal vision, and recent clinical studies have shown that dietary supplementation of ω-6-and ω-3-polyunsaturated fatty acids (PUFAs) can provide a protective role against retinopathy of prematurity (ROP). Our study aims to understand the mechanisms by which altering ω-6-and ω-3-polyunsaturated fatty acids (PUFAs) in the eye can protect against pathologic retinal neovascularization (NV). Methods: We interrogated the effects of endogenous ω-3-PUFA enrichment using transgenic fat-1 mice which convert ω-6-PUFAs to ω-3-PUFAs in the oxygen-induced retinopathy (OIR) murine model. In the OIR model, mice are exposed to 75% oxygen from postnatal day 7 (P7) to P12, then returned to room air (RA). We used a combination of immunofluorescence, bulk retinal RNA sequencing, and lipid mediator profiling by UHPLC-MS/MS in P17 mouse retinas to identify mechanisms underlying the protective effect against NV seen in fat-1 mice exposed to OIR. Results:Fat-1 OIR mice were protected against the development of retinopathy, demonstrating 15.1% less vaso-obliteration (75.5% relative reduction) after OIR and a 6.1% reduction in neovascularization (71.8% relative reduction) at P17 (p < 0.0001 for both). We found a dampened transcriptional response to OIR in the retina of fat-1 mice as compared to WT mouse retinas (198 vs. 782 genes, adjusted p-value < 0.01). Pathway analyses confirmed these findings, with significant OIR-induced transcriptional shifts in angiogenesis (adjusted p-value < 10⁻²⁷), inflammation (adjusted p-value < 10⁻²⁵), and microglial activation pathways (adjusted p-value < 10⁻⁹) in WT mouse retina that were not observed in fat-1 mice. Enrichment scores obtained through the integration of our bulk transcriptomics data with cell-resolved retina data indicate that the protective phenotype observed in fat-1 mice could be associated with intrinsic differences in microglia cell subtypes between WT and fat-1 mice. In situ, WT OIR mice demonstrated an increase in Iba1+ microglia compared to WT RA mice, whereas fat-1 OIR mice showed no difference when compared to fat-1 RA mice. Three ARA-derived oxylipins, 12-hydroxyeicosatetraenoic acid (12-HETE), prostaglandin D2 (PGD2), and thromboxane B2 (TXB2) demonstrated a pattern of upregulation in WT OIR compared to WT RA, but no upregulation in fat-1 OIR mice compared to fat-1 RA. Two EPA-derived specialized pro-resolving mediators and two LA-derived oxylipins were also differentially expressed. Conclusions: These findings show that a lower ω-6:ω-3 protects against neovascularization and is associated with attenuation of hyperoxia-induced microglial recruitment and activation, as well as inflammation and angiogenic signaling. Full article

Lipids are a diverse group of hydrophobic molecules including fats, oils, phospholipids, and steroids that are vital for numerous biological functions including energy storage, cellular structure, and signaling whose composition and metabolism undergo profound transformations with age. These age-related shifts due to increased lipid peroxidation, disrupted cholesterol homeostasis, and altered membrane phospholipid content, actively contribute to progressive loss in cellular homeostasis and pathogenesis of major age-related diseases. This review explores the critical role of lipids: as master regulators of cellular signaling pathways, and as key drivers of chronic inflammation and metabolic dysfunction. Dysregulated lipid metabolism is central to cardiovascular disease which is driven by altered myocardial energy substrate utilization and lipoprotein dynamics. In neurodegenerative disorders like Alzheimer’s and Parkinson’s disease, disruptions in ceramide, cholesterol, and specialized pro-resolving lipid mediators fuel neuroinflammation and protein aggregation. Furthermore, we explore the dual role of dietary lipids, which can either exacerbate or mitigate age-related decline, highlighting the potential of personalized nutritional approaches and lipid-targeting therapeutics. By integrating the mechanisms of lipid signaling, inflammation, and metabolic regulation, this analysis highlights that lipids are not merely passive structural components but active drivers of the aging process, positioning lipid metabolism as a promising frontier for interventions aimed at promoting health span and combating age-related disease. Full article

Curcumin, the major polyphenolic constituent of Curcuma longa, has been widely investigated as a hepatoprotective adjunct due to its antioxidant and immunomodulatory properties. This review evaluates the relevance of curcumin for the prevention and management of liver dysfunction and hepatitis in pigs by synthesizing available porcine evidence and integrating mechanistic insights from translational liver injury models where pig-specific data remain limited. Across experimental hepatic injury contexts, curcumin administration is most consistently associated with reduced biochemical and structural indicators of hepatocellular damage, including decreased aminotransferase activity, attenuation of lipid peroxidation, and enhancement of endogenous antioxidant defenses. These effects are mechanistically linked to suppression of pro-inflammatory signaling pathways, particularly NF-κB-related transcriptional activity and inflammasome-associated responses, together with reduced expression of key cytokines such as TNF-α, IL-1β, and IL-6. Concurrent activation of Nrf2-centered cytoprotective pathways and induction of phase II antioxidant enzymes (including HO-1, GST, and NQO1) appear to constitute a conserved axis supporting hepatic oxidative stress resilience. In swine-relevant infectious settings, available data further support antiviral activity against selected porcine pathogens, including classical swine fever virus and porcine reproductive and respiratory syndrome virus, potentially mediated through interference with lipid-dependent stages of viral replication and modulation of Kupffer cell activation. Although combination strategies with established hepatoprotective approaches are conceptually attractive, current synergy evidence remains heterogeneous and largely extrapolated. Overall, curcumin represents a plausible adjunct candidate for supporting porcine liver health; however, translation into practice will depend on resolving formulation-dependent bioavailability constraints and strengthening the pig-specific evidence base. Full article

Oxidative stress (OS) resulting from an imbalance between reactive oxygen species (ROS) generation and antioxidant defenses plays a pivotal role in vascular diseases such as atherosclerosis and hypertension. ROS derived from NADPH oxidase, mitochondria, and xanthine oxidase promote endothelial dysfunction by inducing lipid and protein oxidation, apoptosis, and pro-inflammatory signaling, thereby enhancing smooth muscle proliferation and atherogenesis. This review summarizes the molecular mechanisms linking OS to vascular injury and aims to systematically elucidate the role of OS in vascular diseases, with a specific focus on critiquing the current challenges in translating biomarkers to clinical practice and the emerging trends in personalized antioxidant therapy. Particular attention is given to biomarkers of oxidative stress, including those assessing antioxidant enzyme activity and oxidative damage products, which possess potential for clinical use. Therapeutic strategies targeting OS, including dietary and pharmacological antioxidants, show promise in improving vascular health, although clinical outcomes have been inconsistent and it is necessary to resolve the standardization and validation of these biomarkers, develop precise targeted therapies against specific ROS sources (e.g., NOX inhibitors, mitochondrial antioxidants), and explore personalized clinical trials based on redox stratification. Overall, OS is a central mediator in vascular pathology, and progress in biomarker validation and targeted therapies will be essential to translate current knowledge into effective prevention, diagnosis, and treatment of cardiovascular diseases. Personalized approaches based on accurate redox profiling may enhance efficacy. Full article

Polyunsaturated fatty acids (PUFAs), particularly omega-3 derivatives such as docosahexaenoic acid (DHA), are precursors of specialized pro-resolving mediators (SPMs) that actively orchestrate the resolution of inflammation. Among these, maresins (MaRs) have gathered increasing attention due to their potent immunomodulatory and tissue-regenerative properties. This review provides a comprehensive synthesis of the current knowledge on the biosynthesis, structural diversity, and biological functions of MaRs, with a focus on MaR1. We discuss the enzymatic pathways involved in the generation of MaR1, MaR2, MaRs conjugates in tissue regeneration (MCTRs), and maresin-like lipid mediators (MaR-Ls), highlighting their roles in modulating inflammatory responses, promoting phagocytosis, and restoring tissue homeostasis. Preclinical evidence from in vitro and in vivo models demonstrates that MaRs exert protective effects in a wide range of pathological contexts, including neuroinflammation, liver injury, cardiovascular dysfunction, pulmonary diseases, and metabolic disorders. Although their therapeutic promise is well-supported, key gaps remain in the understanding of MaRs biosynthesis, receptor specificity, and translational applicability. This review emphasizes the importance of advancing mechanistic and clinical research to fully harness MaRs as part of next-generation therapeutics in inflammation-driven diseases. Full article

Specialized pro-resolving mediators (SPMs), including lipoxins, resolvins, protectins, and maresins, actively terminate inflammation and restore tissue homeostasis. This review addresses how specialized pro-resolving mediators (SPMs) and their omega-3/omega-6 PUFA precursors influence inflammatory pathways, disease mechanisms, and therapeutic potential across major inflammatory skin disorders. MEDLINE/PubMed was searched on 4 October 2025. Eligible studies included experimental, animal, mechanistic human, and interventional research examining SPMs or omega-3/omega-6 fatty acids. Non-English articles, reviews, conference abstracts, and dietary questionnaire–only studies were excluded. Two reviewers independently screened and extracted data. Due to heterogeneity, a narrative synthesis was performed. No formal risk-of-bias assessment was undertaken Of 359 records, 57 studies were included (26 psoriasis, 24 atopic dermatitis, 7 acne; scarce hidradenitis suppurativa data). Preclinical data consistently demonstrated that SPMs modulate key inflammatory pathways, support epithelial repair, and help restore immune balance. Human studies revealed altered cutaneous and systemic lipid mediator profiles—characterized by reduced omega-3–derived SPMs and predominance of omega-6-driven inflammatory mediators—suggesting impaired resolution mechanisms across these disorders. Interventional studies showed that omega-3 supplementation may reduce inflammatory markers, improve barrier function, and alleviate clinical symptoms. Early evidence on SPMs analogues and receptor agonists indicates promising therapeutic potential, but clinical data remain sparse. The body of evidence is limited by scarce human data, small sample sizes, heterogeneous interventions and variable methods. Many studies rely on subjective or non-standardized clinical outcomes, and the predominance of experimental models further limits the translational relevance of current findings. In summary, disturbances in PUFA-derived lipid mediator pathways and insufficient activation of pro-resolving mechanisms may contribute to the persistence of cutaneous inflammation. Omega-3 supplementation and SPMs-based novel therapies therefore represent plausible adjunctive approaches; however, their therapeutic relevance requires confirmation in future mechanistic and clinical studies. Full article

Background/Objectives: Specialized pro-resolving lipid mediators (SPMs), such as Resolvin E1 (RvE1) and Resolvin D1 (RvD1), play a critical role in the resolution phase of inflammation. However, their relevance to tendon pathology and tissue-specific degeneration in rotator cuff tears remains unclear. This study aimed to investigate the relation between serum RvE1 and RvD1 levels and the morphological severity of tendon retraction and muscle fatty degeneration in patients with full-thickness rotator cuff tears. Methods: A total of 70 participants were included: 35 patients with full-thickness rotator cuff tears determined by magnetic resonance imaging (MRI) and 35 healthy controls. Tendon retraction and muscle fatty degeneration were graded using Patte and Goutallier classifications, respectively. Serum RvE1 and RvD1 levels were measured using enzyme-linked immunosorbent assay (ELISA). Group comparisons were performed using Welch’s t-test, and correlations were analyzed with Spearman’s coefficient. Results: RvE1 and RvD1 levels were significantly lower in patients compared to controls (p < 0.001). RvE1 showed a moderate positive correlation with Patte score (ρ = 0.37, p = 0.027), while no significant correlation was observed with Goutallier classification (ρ = 0.19, p = 0.27). RvD1 levels demonstrated no significant relationship with either morphological parameter. Conclusions: These findings suggest that decreased serum RvE1 levels are associated with the severity of tendon retraction but not with muscle fatty degeneration. Therefore, RvE1 may serve as a potential biochemical biomarker reflecting tendon damage severity and the impaired resolution of inflammation in rotator cuff tears. Full article

Oxylipins are specialized lipid mediators that can have dual functions, either promoting inflammation or supporting resolution. Exposure to air pollution is associated with systemic inflammation that may be modified by oxylipins derived from polyunsaturated fatty acids (FA). In this study, we examined whether short-term air pollution exposure is associated with changes in circulating oxylipins in healthy adults, who were on high- or low-dietary omega-3 fatty acid (n-3 FA) intakes. We measured 56 oxylipin species from participants’ plasma samples and employed mixed-effects models to assess the associations, stratified by n-3 FA groups. Plasma concentrations of oxylipins derived from n-3 FA [e.g., 14-hydroxydocosahexaenoic acid (14-HDHA) & 11-hydroxydocosahexaenoic acid (11-HDoHE), and 12-hydroxyeicosapentaenoic acid (12-HEPE)] were significantly higher in the high n-3 FA group compared to the low group. Conversely, selected oxylipins derived from n-6 FA [e.g., 15-hydroxyeicosatetraenoic acid (15-HETE) and 14,15-Dihydroxyeicosatrienoic acid (14,15-DiHETrE)] were significantly lower in the high n-3 group. Exposure to PM_2.5, O₃, and NO₂ was associated with reductions in pro-inflammatory oxylipins produced by lipoxygenase in the high n-3 FA group, but not in the low group; for example, 12-HETE. Furthermore, participants in the high n-3 group exposed to PM_2.5, O₃, and NO₂ had elevated levels of n-3 FA-derived pro-resolving oxylipins compared to those in the low n-3 group; for instance, 12-HEPE and 14-HDHA & 11-HDoHE. In conclusion, short-term air pollution exposure was associated with lower pro-inflammatory and higher pro-resolving oxylipin levels in the high n-3 FA group. These findings suggest n-3-derived lipid metabolites may promote inflammation resolution induced by air pollution. Full article

Dilated cardiomyopathy is a major cause of heart failure and is one of the most common forms of cardiomyopathy worldwide. Although there has been significant progress in its clinical management, early diagnosis and precise prognosis remain challenging due to the lack of specificity in current biomarkers. As inflammation plays a key role in DCM, we determined the levels of systemic inflammatory markers and specific pro-resolving lipid mediators (SPMs) in a cohort of DCM patients. Our data show that the levels of lipoxin A4 significantly increased in DCM patients (343 + 75.1 pg/mL in controls vs. 482.2 ± 159.1 pg/mL in DCM patients), whereas the opposite was observed for resolving D1 (57.18 ± 32.68 pg/mL in controls vs. 38.55 ± 25.13 pg/mL in DCM patients). These results may indicate that SPMs could be considered new biomarkers related to the progression of this pathology. Moreover, since microRNAs (miRNAs) are also considered potential biomarkers at the molecular level, we conducted comprehensive miRNA expression profiling using a high-throughput array platform in our cohort. Of the differentially expressed miRNAs identified, we chose to focus on two that were significantly upregulated (miR378-3p and miR486-5p; more than two-folds) or downregulated (miR142-3p and miR328-3p < 20% and 40% vs. the control, respectively) in DCM patients, all of them strongly associated with inflammatory pathways. The selected miRNAs showed considerable potential as biomarkers, exhibiting statistical significance after ROC analysis. In fact, improved performance was observed when combining both miR142-3p and miR328-3p, using a LASSO regression model. However, we found no correlation between miRNAs and traditional inflammatory markers or SPMs ruling out the possibility to proposing them as combined biomarkers in this case. The heterogeneity of DCM leads to the need to identify new biomarkers that, either individually or in combination, may improve the prognosis of affected individuals. In our study, we have identified that some of the main SPMs can provide valuable information about disease progression, in addition to the combination of certain circulating miRNAs, which show promising prognostic values in our cohort. Thus, we have identified novel biomarkers that integrate inflammatory profiles with specific circulating miRNA expression patterns is an important step towards more targeted patient stratification in DCM. This approach can improve DCM diagnosis and prognosis, supporting the development of personalized treatments through a multi-parameter panel of biomarkers that can be measured in peripheral blood and used in routine clinical practice. Such a strategy can enable earlier treatment, resulting in better patient outcomes and quality of life. Full article

Severe Coronavirus disease 2019 (COVID-19) is associated with abnormal innate and adaptive immune responses, as well as systemic alterations, including a shift in lipid network. A case–control study was conducted to describe the systemic lipidomic profile in COVID-19 according to disease severity. Selected polyunsaturated fatty acids (PUFAs), oxylipins, and endocannabinoids were analysed using a targeted liquid chromatography coupled to mass spectrometry in tandem method. Multivariate receiver operating characteristic curve-based model evaluation was performed to define a lipidomic signature for the disease. A total of 135 hospitalized COVID-19 patients, of whom 85 had severe form, and 134 healthy individuals were included. Patients exhibited increased levels of free PUFAs, proinflammatory and pro-resolving oxylipins, and endocannabinoids compared to controls. A combination of five lipid mediators, i.e., prostaglandin D2, prostaglandin E2, thromboxane B2, lipoxin B4, and 2-archidonylglycerol, discriminates patients from control individuals with excellent accuracy [AUC, 0.977 (0.950–0.995)]. The severe form is characterized by an imbalance between proinflammatory and pro-resolving oxylipins and increased endocannabinoids. COVID-19 is associated with a lipid storm that conditions disease severity. Targeting lipid mediators-related metabolic and signalling pathways could be an interesting therapeutic option in severe forms. Full article

Osteoarthritis (OA), the most prevalent form of arthropathy, is characterized by progressive degradation of cartilage, synovial inflammation, and other pathological changes that gradually affect the entire joint. Once regarded as a purely degenerative disease with minimal immune involvement, recent evidence reveals that chronic low-grade inflammation, insidiously fueled by the destructive crosstalk between cartilage and synovium, plays a key role in OA pathophysiology. Among the immune cells involved, eosinophils have emerged as unexpected yet significant contributors, exhibiting both pro-inflammatory and immunoregulatory properties. Traditionally associated with allergic responses and antiparasitic defense, eosinophils can also secrete anti-inflammatory cytokines along with specialized pro-resolving lipid mediators (SPMs) that promote macrophage polarization toward reparative M2 phenotypes. Eosinophils may sustain inflammation or, conversely, act as “silent modulators” that subtly shape the immune microenvironment and support tissue homeostasis. This immunological plasticity positions them at the intersection of joint damage and repair. This article explores emerging evidence on eosinophil activity in OA, emphasizing their dual nature and potential as therapeutic targets to shift the joint milieu from a pro-inflammatory state toward resolution. Understanding eosinophil-mediated pathways may pave the way for novel strategies to reduce synovial inflammation, preserve cartilage integrity, and improve clinical outcomes. Full article