Search Results (33)

Background: The anti-inflammatory effects of omega-3 fatty acids and their derivatives are of considerable interest as a potential therapeutic agent in many diseases characterized by inflammation. Methods: This study aimed to measure the concentration of mediators derived from eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids. We included 33 women suffering from Hashimoto’s disease, with an average age of 37.58 ± 8.41 kg, in the study. The levels of EPA and DHA acids were examined using gas chromatography, and their derivatives were studied with liquid chromatography (HPLC). Patients were assessed after being put on a healthy and balanced diet supplemented with omega-3 fatty acids. Results: The results showed statistically significant correlations between the C-reactive protein (CRP) level and derivatives: resolvins E1 and D1 (RvE1, RvD1), 10S17R DiHDHA (Protectin DX), and 18RS HEPE (18-hydro(peroxy)-eicosapentaenoic acid) following the diet. There was also a significant correlation observed between Maresin 1 and free thyroxine (fT4). Moreover, a dependency between the RvD1 level and some anthropometric parameters was observed. Conclusions: The findings suggest that the chronic inflammatory state occurring in the course of Hashimoto’s thyroiditis (HT) is associated with increased synthesis of anti-inflammatory mediators of omega-3 fatty acids, particularly DHA derivatives. Consequently, these may affect the level of thyroid hormone synthesis, which should be considered in future research on biological drugs in Hashimoto’s therapy. Full article

Background: Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been used in the treatment of inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS), and their effects are potentiated upon conversion to specialized pro-resolving mediators (SPM). Recent studies indicated that the probiotic bacterial strain Bacillus megaterium DSM 32963 can be used to enhance the production of SPM and its precursors in vivo. Methods: Here, we explored the contribution of Bacillus megaterium DSM 32963 to SPM production in a validated, dynamic model of the upper and lower intestine. The TIM-1 and TIM-2 models were applied, with the TIM-2 model inoculated with the fecal microbiota of healthy individuals and probed with an n-3 PUFA lysine salt with and without Bacillus megaterium DSM 32963 or an SPM-enriched fish oil or placebo. Kinetics of SPM production were assessed by metabololipidomics analysis, and survival and engraftment of the Bacillus megaterium strain was monitored by plate counting and by strain-specific qPCR. Results: Bacillus megaterium DSM 32963 poorly survived TIM-1 conditions but propagated in the TIM-2 model, where it enabled the metabolism of n-3 PUFA to SPM (resolvin E2 and protectin DX) and SPM precursors (e.g., 5-hydroxyeicosapentaenoic acid (5-HEPE), 15-HEPE, 18-HEPE, 4-hydroxydocosahexaenoic acid (4-HDHA), 10-HDHA, and 17-HDHA, among other EPA- and DHA-derived metabolites) with significantly higher levels of lipid mediator production compared to the n-3 PUFA lysine salt alone; esterified n-3 PUFA were hardly converted by the microbiota. Conclusions: These findings reinforce that Bacillus megaterium DSM 32963 facilitates SPM production in situ from bioavailable n-3 PUFA in the large intestine, highlighting its use to complement eukaryotic SPM biosynthesis by the host and its possible therapeutic use for, e.g., IBD and IBS. Full article

The potential modulation of thyroid inflammatory conditions via a gluten-free diet has been suggested after establishing a link between Hashimoto’s thyroiditis (HT) and celiac disease. However, the majority of targeted studies in this field do not support the general recommendation of prescribing a gluten-free diet (GFD) for all HT patients. This study aims to analyze data regarding the impact of a GFD supplemented with eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), along with vegetables, on the course of inflammation involving long-chain fatty acid mediators. The study cohort consisted of 39 Caucasian female patients with autoimmune HT. Metabolite separations were performed using a liquid chromatograph with a DAD detector. Absorption peaks were read at 210 nm for resolvin E1, protectin DX, and maresin 1 and at 302 nm for resolvin D1. The introduction of a gluten-free diet completed with omega-3, including EPA and DHA, may contribute to a reduction in the inflammatory state in HT patients. This effect is supported by the elevation in the levels of anti-inflammatory mediators derived from long-chain fatty acids with anti-inflammatory properties but not by eliminating gluten. Significant statistical changes in the levels of all derivatives were observed before and after the implementation of the diet. It is worth noting that this effect was not observed in anti-TPO and anti-TG levels. The induction of anti-inflammatory changes can be achieved by supplementing the diet with EPA, DHA and vegetables with increased anti-inflammatory potential. Full article

Individuals with chronic diseases are more vulnerable to environmental inhalation exposures. Although metabolic syndrome (MetS) is increasingly common and is associated with susceptibility to inhalation exposures such as particulate air pollution, the underlying mechanisms remain unclear. In previous studies, we determined that, compared to a healthy mouse model, a mouse model of MetS exhibited increased pulmonary inflammation 24 h after exposure to AgNPs. This exacerbated response was associated with decreases in pulmonary levels of specific specialized pro-resolving mediators (SPMs). Supplementation with specific SPMs that are known to be dysregulated in MetS may alter particulate-induced inflammatory responses and be useful in treatment strategies. Our current study hypothesized that administration of resolvin E1 (RvE1), protectin D1 (PD1), or maresin (MaR1) following AgNP exposure will differentially regulate inflammatory responses. To examine this hypothesis, healthy and MetS mouse models were exposed to either a vehicle (control) or 50 μg of 20 nm AgNPs via oropharyngeal aspiration. They were then treated 24 h post-exposure with either a vehicle (control) or 400 ng of RvE1, PD1, or MaR1 via oropharyngeal aspiration. Endpoints of pulmonary inflammation and toxicity were evaluated three days following AgNP exposure. MetS mice that were exposed to AgNPs and received PBS treatment exhibited significantly exacerbated pulmonary inflammatory responses compared to healthy mice. In mice exposed to AgNPs and treated with RvE1, neutrophil infiltration was reduced in healthy mice and the exacerbated neutrophil levels were decreased in the MetS model. This decreased neutrophilia was associated with decreases in proinflammatory cytokines’ gene and protein expression. Healthy mice treated with PD1 did not demonstrate alterations in AgNP-induced neutrophil levels compared to mice not receiving treat; however, exacerbated neutrophilia was reduced in the MetS model. These PD1 alterations were associated with decreases in proinflammatory cytokines, as well as elevated interleukin-10 (IL-10). Both mouse models receiving MaR1 treatment demonstrated reductions in AgNP-induced neutrophil influx. MaR1 treatment was associated with decreases in proinflammatory cytokines in both models and increases in the resolution inflammatory cytokine IL-10 in both models, which were enhanced in MetS mice. Inflammatory responses to particulate exposure may be treated using specific SPMs, some of which may benefit susceptible subpopulations. Full article

Non-steroidal anti-inflammatory drugs (NSAIDs), the most highly prescribed drugs in the world for the treatment of pain, inflammation, and fever, cause gastric mucosal damage, including ulcers, directly or indirectly, by which the development of GI-safer (-sparing) NSAIDs relates to unmet medical needs. This study aimed to document the preventive effects of walnut polyphenol extracts (WPEs) against NSAID-induced gastric damage along with the molecular mechanisms. RGM-1 gastric mucosal cells were administered with indomethacin, and the expressions of the inflammatory mediators between indomethacin alone or a combination with WPEs were compared. The expressions of the inflammatory mediators, including COX-1 and COX-2, prostaglandin E², 15-hydroxyprostaglandin dehydrogenase (15-PGDH), and antioxidant capacity, were analyzed by Western blot analysis, RT-PCR, and ELISA, respectively. HO-1, Nrf-2, and keap1 were investigated. The in vivo animal models were followed with in vitro investigations. The NSAIDs increased the expression of COX-2 and decreased COX-1 and 15-PGDH, but the WPEs significantly attenuated the NSAID-induced COX-2 expression. Interestingly, the WPEs induced the expression of 15-PGDH. By using the deletion constructs of the 15-PGDH promoter, we found that c-Jun is the most essential determinant of the WPE-induced up-regulation of 15-PGDH expression. We confirmed that the knockdown of c-Jun abolished the ability of the WPEs to up-regulate the 15-PGDH expression. In addition, the WPEs significantly increased the HO-1 expression. The WPEs increased the nuclear translocation of Nrf2 by Keap-1 degradation, and silencing Nrf2 markedly reduced the WPE-induced HO-1 expression. We found that the WPE-induced HO-1 up-regulation was attenuated in the cells harboring the mutant Keap1, in which the cysteine 151 residue was replaced by serine. These in vitro findings were exactly validated in indomethacin-induced gastric rat models. Daily walnut intake can be a promising nutritional supplement providing potent anti-inflammatory, antioxidative, and mucosa-protective effects against NSAID-induced GI damage. Full article

Periodontal disease is characterized by inflammation and bone loss. Central to its pathogenesis is the dysregulated inflammatory response, complicating regenerative therapies. Mesenchymal stem cells (MSCs) hold significant promise in tissue repair and regeneration. This study investigated the effects of specialized pro-resolving mediators (SPMs), Resolvin E1 (RvE1) and Maresin 1 (MaR1), on the osteogenic differentiation of human bone marrow-derived MSCs under inflammatory conditions. The stem cells were treated with SPMs in the presence of lipopolysaccharide (LPS) to simulate an inflammatory environment. Osteogenic differentiation was assessed through alkaline phosphatase activity and alizarin red staining. Proteomic analysis was conducted to characterize the protein expression profile changes, focusing on proteins related to osteogenesis and osteoclastogenesis. Treatment with RvE1 and MaR1, both individually and in combination, significantly enhanced calcified deposit formation. Proteomic analysis revealed the differential expression of proteins associated with osteogenesis and osteoclastogenesis, highlighting the modulatory impact of SPMs on bone metabolism. RvE1 and MaR1 promote osteogenic differentiation of hBMMSCs in an inflammatory environment, with their combined application yielding synergistic effects. This study provides insights into the therapeutic potential of SPMs in enhancing bone regeneration, suggesting a promising avenue for developing regenerative therapies for periodontal disease and other conditions characterized by inflammation-induced bone loss. Full article

Both honey and fish oil have been historically used in medicine and identified as having antimicrobial properties. Although analyses of the substances have identified different components within them, it is not fully understood how these components interact and contribute to the observed effect. With the increase in multi-drug resistant strains of bacteria found in infections, new treatment options are needed. This study aimed to assess the antimicrobial abilities of fish oil components, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and derived resolvins (RvE1, RvD2, and RvD3), as well as two varieties of manuka honey, against a panel of medically relevant microorganisms and antimicrobial resistant organisms, such as Methicillin Resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Escherichia coli. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were identified; further minimum biofilm eradication concentrations (MBEC) were investigated for responsive organisms, including S. aureus, E. coli, Staphylococcus epidermidis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Concurrent with the existing literature, manuka honey was found to be a broad-spectrum antimicrobial with varied potency according to methylglyoxal content. DHA and EPA were both effective against Gram-positive and negative bacteria, but some drug-resistant strains or pathogens were not protected by a capsule. Only E. coli was inhibited by the resolvins. Full article

Space-related stressors such as microgravity are associated with cellular and molecular alterations of the immune and inflammatory homeostasis that have been linked to the disorders that astronauts suffer from during their missions. Most of the research of the past 30 years has consistently established that innate adaptive immune cells represent a target of microgravity, which leads to their defective or dysfunctional activation, as well as to an altered ability to produce soluble mediators—e.g., cytokines/chemokines and bioactive lipids—that altogether control tissue homeostasis. Bioactive lipids include a vast array of endogenous molecules of immune origin that control the induction, intensity and outcome of the inflammatory events. However, none of the papers published so far focus on a newly characterized class of lipid mediators called specialized pro-resolving mediators (SPMs), which orchestrate the “resolution of inflammation”—i.e., the active control and confinement of the inflammatory torrent mostly driven by eicosanoids. SPMs are emerging as crucial players in those processes that avoid acute inflammation to degenerate into a chronic event. Given that SPMs, along with their metabolism and signaling, are being increasingly linked to many inflammatory disorders, their study seems of the outmost importance in the research of pathological processes involved in space-related diseases, also with the perspective of developing therapeutic countermeasures. Here, we show that microgravity, simulated in the rotary cell culture system (RCCS) developed by NASA, rearranges SPM receptors both at the gene and protein level, in human monocytes but not in lymphocytes. Moreover, RCCS treatment reduces the biosynthesis of a prominent SPM like resolvin (Rv) D1. These findings strongly suggest that not only microgravity can impair the functioning of immune cells at the level of bioactive lipids directly involved in proper inflammation, but it does so in a cell-specific manner, possibly perturbing immune homeostasis with monocytes being primary targets. Full article

Background: Pregnancy is a physiological state during which inflammation occurs. This complex biological response is necessary for the implantation process as well as delivery. In turn, its suppression during gestation favors the normal course of the pregnancy. Therefore, the presence of pro-resolving mediators, EPA and DHA derivatives, The aim of this study was to investigate the changes in the levels of anti-inflammatory resolvins and their precursors in different trimesters of pregnancy with consideration of the women’s weight, including overweight and obese women before pregnancy. Methods: A total of 78 women participated in this study; the mean age and BMI before pregnancy were 32.3 ± 5.52 and 27.73 ± 6.13, respectively. The patients were divided into two groups, considering their BMI before pregnancy. The extraction of eicosanoids was performed by high-performance liquid chromatography. The results obtained were subjected to statistical analysis. The levels of all studied parameters showed statistically significant differences between the study group (SG) and the control group (CG) in the different trimesters of pregnancy. Over the course of pregnancy, the levels of protection (PDX), maresin, resolvins (RvD1, RvE1), and their precursors differed in relation to the trimester of pregnancy and the division into groups considering the correct body weight before pregnancy. Results: Overweight or obese women had significantly lower levels of RvE1 in the third trimester and their precursors compared to normal-weight women. While the levels of PDX and RvD1 were significantly higher, this may be due to both a lower intake of products rich in omega-3 fatty acids by obese women and an increased need of obese women’s bodies to quench chronic inflammatory processes associated with obesity. Conclusions: Both EPA and DHA derivatives are involved in calming down inflammation during pregnancy, which was observed. Full article

Specialized pro-resolving mediators (SPMs) and especially Resolvin E1 (RvE1) can actively terminate inflammation and promote healing during lung diseases such as acute respiratory distress syndrome (ARDS). Although ARDS primarily affects the lung, many ARDS patients also develop neurocognitive impairments. To investigate the connection between the lung and brain during ARDS and the therapeutic potential of SPMs and its derivatives, fat-1 mice were crossbred with RvE1 receptor knockout mice. ARDS was induced in these mice by intratracheal application of lipopolysaccharide (LPS, 10 µg). Mice were sacrificed at 0 h, 4 h, 24 h, 72 h, and 120 h post inflammation, and effects on the lung, liver, and brain were assessed by RT-PCR, multiplex, immunohistochemistry, Western blot, and LC-MS/MS. Protein and mRNA analyses of the lung, liver, and hypothalamus revealed LPS-induced lung inflammation increased inflammatory signaling in the hypothalamus despite low signaling in the periphery. Neutrophil recruitment in different brain structures was determined by immunohistochemical staining. Overall, we showed that immune cell trafficking to the brain contributed to immune-to-brain communication during ARDS rather than cytokines. Deficiency in RvE1 receptors and enhanced omega-3 polyunsaturated fatty acid levels (fat-1 mice) affect lung–brain interaction during ARDS by altering profiles of several inflammatory and lipid mediators and glial activity markers. Full article

Resolvin E1 is a metabolite of eicosapentaenoic acid (EPA) which is one of the omega-3 polyunsaturated fatty acids (omega-3 PUFAs). The antiplatelet properties of omega-3 PUFAs are well known, but the effect of resolvin E1 on platelets via the collagen receptors is extremely poorly reported. We investigated the effect of resolvin E1 on collagen-induced platelet aggregation, activation, and reactivity, and also platelet membrane fluidity. The ultimate and statistically significant results showed that resolvin E1 may inhibit platelet reactivity due to the reduction of collagen-induced platelet aggregation in platelet-rich plasma and isolated platelets, but not in whole blood. Also, resolvin E1 significantly reduced P-selectin exposure on collagen-stimulated platelets. Moreover, we demonstrated that resolvin E1 can maintain platelet membrane structure (without increasing membrane fluidity). The association between platelet reactivity and membrane fluidity, including resolvin E1 and collagen receptors requires further research. However, the goal of this study was to shed light on the molecular mechanisms behind the anti-aggregative effects of resolvin E1 on platelets, which are still not fully clarified. We also indicate an innovative research direction focused on further analysis and then use of omega-3 PUFAs metabolites as antiplatelet compounds for future applications in the treatment and prevention of cardiovascular diseases. Full article

Uncontrolled diabetes is characterized by aberrant inflammatory reactions and increased collagenolysis. We have reported that it accelerates the degradation of implanted collagen membranes (CM), thus compromising their function in regenerative procedures. In recent years, a group of physiological anti-inflammatory agents called specialized pro-resolving lipid mediators (SPMs) have been tested as a treatment for various inflammatory conditions, either systemically or locally, via medical devices. Yet, no study has tested their effect on the fate of the biodegradable material itself. Here, we measured the in vitro release over time of 100 or 800 ng resolvin D1 (RvD1) incorporated into CM discs. In vivo, diabetes was induced in rats with streptozotocin, while buffer-injected (normoglycemic) rats served as controls. Resolvins (100 or 800 ng of RvD1 or RvE1) were added to biotin-labeled CM discs, which were implanted sub-periosteally over the calvaria of rats. Membrane thickness, density, and uniformity were determined by quantitative histology after 3 weeks. In vitro, significant amounts of RvD1 were released over 1–8 days, depending on the amount loaded. In vivo, CMs from diabetic animals were thinner, more porous, and more variable in thickness and density. The addition of RvD1 or RvE1 improved their regularity, increased their density, and reduced their invasion by the host tissue significantly. We conclude that addition of resolvins to biodegradable medical devices can protect them from excessive degradation in systemic conditions characterized by high degree of collagenolysis. Full article

Resolvin E1 (RvE1) is an eicosapentaenoic acid-derived lipid mediator involved in the resolution of inflammation. Here, we investigated whether RvE1 alterations may occur in an animal model of age-related macular degeneration (AMD). To this end, Sprague Dawley albino rats underwent light damage (LD), and retinas and serum were analyzed immediately or seven days after treatment. Western blot of retinas showed that the RvE1 receptor ChemR23 and the RvE1 metabolic enzymes 5-LOX and COX-2 were unchanged immediately after LD, but they were significantly up-regulated seven days later. Instead, the RvE1 receptor BLT1 was not modulated by LD, and neither was the RvE1 degradative enzyme 15-PGDH. Moreover, ChemR23, 5-LOX, COX-2 and BLT1 were found to be more expressed in the inner retina under all experimental conditions, as observed through ImageJ plot profile analysis. Of note, amacrine cells highly expressed BLT1, while ChemR23 was highly expressed in the activated microglia of the outer retina. ELISA assays also showed that LD rats displayed significantly higher circulating levels and reduced retinal levels of RvE1 compared to controls. Altogether, our data indicate that RvE1 metabolism and signaling are modulated in the LD model, suggesting a potentially relevant role of this pathway in AMD. Full article

Particulate matter in the air exacerbates airway inflammation (AI) in asthma; moreover, prenatal exposure to concentrated urban air particles (CAPs) and diesel exhaust particles (DEPs) predisposes the offspring to asthma and worsens the resolution of AI in response to allergens. We previously tested the hypothesis that such exposure impairs the pathways of specialized proresolving mediators that are critical for resolution and found declined Lipoxin A4 (LxA4) and Resolvin E2 (RvE2) levels in the “at-risk” pups of exposed mothers. Here, we hypothesized that supplementation with synthetic LxA4 or RvE2 via the airway can ameliorate AI after allergen exposure, which has not been tested in models with environmental toxicant triggers. BALB/c newborns with an asthma predisposition resultant from prenatal exposure to CAPs and DEPs were treated once daily for 3 days with 750 ng/mouse of LxA4 or 300 ng/mouse of RvE2 through intranasal instillation, and they were tested with the intentionally low-dose ovalbumin protocol that elicits asthma in the offspring of particle-exposed mothers but not control mothers, mimicking the enigmatic maternal transmission of asthma seen in humans. LxA4 and RvE2 ameliorated the asthma phenotype and improved AI resolution, which was seen as declining airway eosinophilia, lung tissue infiltration, and proallergic cytokine levels. Full article

An interconnection between tissue inflammation and regeneration has been established through the regulation of defense and repair mechanisms within diseased dental tissue triggered by the release of immune-resolvent mediators. To better our understanding of the role of specific pro-resolving mediators (SPMs) in inflamed human bone marrow-derived mesenchymal stem cells (hBMMSCs), we studied the effects of Resolvin E1 (RvE1) and Maresin 1 (MaR1) in lipopoly-saccharide (LPS) stimulated hBMMSCs. The hBMMSCs were divided into five different groups, each of which was treated with or without SPMs. Group-1: negative control (no LPS stimulation), Group-2: positive control (LPS-stimulated), Group-3: RvE1 100 nM + 1 μg/mL LPS, Group-4: MaR1 100 nM + 1 µg/mL LPS, and Group-5: RvE1 100 nM + MaR1100 nM + 1 μg/mL LPS. Cell proliferation, apoptosis, migration, colony formation, Western blotting, cytokine array, and LC/MS analysis were all performed on each group to determine the impact of SPMs on inflammatory stem cells. According to our data, RvE1 plus MaR1 effectively reduced inflammation in hBMMSCs. In particular, IL-4, 1L-10, and TGF-β1 activation and downregulation of RANKL, TNF-α, and IFN-γ compared to groups receiving single SPM were shown to be significantly different (Group 3 and 4). In addition, the LC/MS analysis revealed the differentially regulated peptide’s role in immunological pathways that define the cellular state against inflammation. Inflamed hBMMSCs treated with a combination of Resolvin E1 (RvE1) and Maresin 1 (MaR1) promoted the highest inflammatory resolution compared to the other groups; this finding suggests a potential new approach of treating bacterially induced dental infections. Full article