Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, arise from various factors such as dietary, genetic, immunological, and microbiological influences. The gut microbiota plays a crucial role in the development and treatment of IBD, though the exact mechanisms remain uncertain. Current research has yet to definitively establish the beneficial effects of the microbiome on IBD. Bacteria and viruses (both prokaryotic and eukaryotic) are key components of the microbiome uniquely related to IBD. Numerous studies suggest that dysbiosis of the microbiota, including bacteria, viruses, and bacteriophages, contributes to IBD pathogenesis. Conversely, some research indicates that bacteria and bacteriophages may positively impact IBD outcomes. Additionally, plant metabolites play a crucial role in alleviating IBD due to their anti-inflammatory and microbiome-modulating properties. This systematic review discusses the role of the microbiome in IBD pathogenesis and evaluates the potential connection between plant metabolites and the microbiome in the context of IBD pathophysiology.

Patent ductus arteriosus (PDA) is a common congenital heart defect in preterm infants and is associated with significant morbidity. Early diagnosis is crucial but challenging due to nonspecific clinical symptoms. This study aims to identify potential metabolomic biomarkers for early detection of PDA using human cord blood. A prospective cross-sectional study was conducted involving 45 preterm infants between 230/6 and 316/7 weeks of gestation. The diagnosis of hemodynamically significant PDA (hsPDA) was based on echocardiographic findings after 48 h, showing a left atrium-to-aortic root ratio > 1.5 and/or a ductus diameter > 1.5 mm. Untargeted metabolomics analysis was performed on cord blood plasma samples using quadrupole time-of-flight liquid chromatography-mass spectrometry (Q-TOF LC/MS). Data were processed for metabolites that differed between groups. Twenty infants with hsPDA formed the study group, 25 controls. Out of 4237 detected peaks, 40 showed statistically significant differences (fold change > 1.5,p < 0.05). Among these, 15 metabolites were potentially clinically relevant. Key findings included decreased levels of guanidino acetic acid, S-adenosylmethionine, and ceramides and increased levels of docosahexaenoic acid, arachidonic acid, and cholesterol-related molecules in the PDA group. The study reveals significant metabolic alterations in lipid metabolism and oxidative stress-related pathways in PDA infants. Further targeted metabolomics studies are warranted to validate and explore clinical applications.

Oxylipins are polyunsaturated fatty acid (PUFA)-derived inflammatory mediators, and include both pro-inflammatory (prostaglandins, thromboxane, leukotrienes), and pro-resolving (lipoxins, E-resolvins, D-resolvins, protectins, maresins) molecules. Sickle cell disease (SCD) is an inflammatory pathology. We profiled plasma oxylipins in SCD (n = 45) and control children (n = 24), and evaluated their associations with inflammatory biomarkers, and SCD clinical history. We demonstrated the presence of PGE2, TxB2, RvE2, RvD1, AT-RvD3, and numerous monohydroxy-PUFAs in both SCD and control plasma. Levels of TxB2, RvD1, 12-HETE, 5-HEPE, and 7-HDoHE were significantly increased in SCD. 12-HETE and 5-HEPE correlated positively with IL-6 and IL-1β, respectively, while 15-HETE negatively associated with soluble-ICAM-1. 7-HDoHE levels were significantly lower in children with a history of VOC and ACS compared to those without any clinical complications. Since RvD1 is a pro-resolving mediator, the observed increase in RvD1 in SCD may reflect a host mechanism attempting to mitigate disease-associated chronic inflammation by promoting resolution of inflammation.

Depression is a globally prevalent emotional disorder with a complex pathophysiology. Microglia are resident immune cells in the central nervous system, playing crucial roles in regulating inflammation, synaptic plasticity, immune phagocytosis, and other functions, thereby exerting significant impacts on neuropsychiatric disorders like depression. Increasing research indicates that abnormal phagocytic function of microglia in the brain is involved in depression, showing excessive or insufficient phagocytosis in different states. Here, we have provided a review of the signaling molecules involved in microglial phagocytosis in depression, including "eat me" signals such as phosphatidylserine (PS), complement, and "don't eat me" signals such as CD47, CD200 and related receptors. Furthermore, we discuss the regulatory effects of existing pharmaceuticals and dietary nutrients on microglial phagocytosis in depression, emphasizing the need for tailored modulation based on the varying phagocytic states of microglia. This review aims to facilitate a deeper understanding of the role of microglial phagocytosis in depression and provide a roadmap for potential therapeutic strategies for depression targeting microglial phagocytosis.

Cardiovascular disease is one of the leading causes of death worldwide. Even while receiving adequate pharmacological treatment for their hypertension, people are nonetheless at greater risk for cardiovascular disease. There is growing evidence that the gut microbiota may have major positive and negative effects on blood pressure and illnesses related with it as more study into this topic is conducted. Trimethylamine n-oxide (TMAO) and short-chain fatty acids (SCFA) are two major by-products of the gut microbiota. TMAO is involved in the formation of other coronary artery diseases, including atherosclerosis and hypertension, while SCFAs play an important role in controlling blood pressure. Numerous investigations have confirmed the established link between dietary salt intake and hypertension. Reducing sodium in the diet is linked to lower rates of cardiovascular disease morbidity and mortality as well as lower rates of blood pressure and hypertension. In both human and animal research, high salt diets increase local and systemic tissue inflammation and compromise gut architecture. Given that the gut microbiota constantly interacts with the immune system and is required for the correct maturation of immune cells, it is scientifically conceivable that it mediates the inflammatory response. This review highlights the therapeutic possibilities for focusing on intestinal microbiomes as well as the potential functions of the gut microbiota and its metabolites in the development of hypertension.

We examined associations between lipidomic profiles and incident ischemic stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Plasma lipids (n = 195) were measured from baseline blood samples, and lipids were consolidated into underlying factors using exploratory factor analysis. Cox proportional hazards models were used to test associations between lipid factors and incident stroke, linear regressions to determine associations between dietary intake and lipid factors, and the inverse odds ratio weighting (IORW) approach to test mediation. The study followed participants over a median (IQR) of 7 (3.4-11) years, and the case-cohort substudy included 1075 incident ischemic stroke and 968 non-stroke participants. One lipid factor, enriched for docosahexaenoic acid (DHA, an omega-3 fatty acid), was inversely associated with stroke risk in a base model (HR = 0.84; 95%CI 0.79-0.90; P = 8.33 × 10-8) and fully adjusted model (HR = 0.88; 95%CI 0.83-0.94; P = 2.79 × 10-4). This factor was associated with a healthy diet pattern (β = 0.21; 95%CI 0.12-0.30; P = 2.06 × 10-6), specifically with fish intake (β = 1.96; 95%CI 0.95-2.96; P = 1.36 × 10-4). DHA was a mediator between fish intake and incident ischemic stroke (30% P = 5.78 × 10-3). Taken together, DHA-containing plasma lipids were inversely associated with incident ischemic stroke and mediated the relationship between fish intake and stroke risk.

The effects of nutritional supplements and dietary interventions on rheumatoid arthritis (RA) are still unclear.

This study aimed to evaluate the impact of nutritional supplements and dietary interventions on RA patients.

The online databases of PubMed, Web of Science, Embase, and Cochrane Library were used to search the relevant literature from inception to December 2024. Meta-analyses with the inclusion of randomized controlled trials were selected to assess the effects of nutritional supplements or dietary interventions on RA. We accessed the methodological quality of included reviews using AMSTAR 2 and evaluated the quality of evidence for intervention effects using GRADE. Data synthesis and analysis were used by R 4.4.1 and STATA 17.

A total of 14 articles were included, evaluating the effects of nutritional supplements and dietary interventions on RA management. Among these, 3 studies were rated as high quality, 6 as low quality, and 5 as critically low quality by AMSTAR2. The quality of evidence for intervention effects ranges from low to very low quality. The interventions assessed included polyunsaturated fatty acids (PUFAs), probiotics, total glucosides of paeony (TGP), anti-inflammatory diets (AIDs), and others. TGP was the only intervention to significantly reduce both the disease activity score and erythrocyte sedimentation rate, although the quality of evidence for these effects was low. Probiotics contributed to significant reductions in C-reactive protein and visual analogue scale scores, with both outcomes rated as low quality. PUFAs demonstrated significant improvements in tender joint count, swollen joint count, and morning stiffness, though, like the other interventions, these effects were also rated as low quality.

There was relatively strong evidence supporting that PUFAs, probiotics, TGP, and AIDs may show some benefits on RA. However, the low quality of evidence highlights the need for further high-quality research and real-world evidence to confirm their effectiveness.

Cyanobacterial extracts offer significant potential for the development of new natural antioxidants and biologically active compounds with applications in various industries. Data on the genus Tolypothrix are limited; therefore, the aim of the present study was to investigate the anticancer, antioxidant and anti-inflammatory activity of extracts prepared from strains of this genus. Cytotoxicity and anticancer activity were evaluated by in vitro tests with four cell lines using the MTT assay. The assessment of antioxidant activity was performed by the DPPH and ABTS methods in combination with the calculation of the total phenolic content. Anti-inflammatory activity was investigated using the LPS-stimulated macrophage model (RAW264.7) and subsequent measurement of the levels of secreted cytokines IL-6 and TNF-α. The lipid content and fatty acid composition of the non-polar extracts were determined by gas chromatography (GC). To elucidate the mechanism of cytotoxicity/anticancer action of the non-polar extracts, the effects of stearidonic acid, which was detected in four of the studied cyanobacterial strains, were additionally tested on the same cell lines. A molecular docking analysis was performed simulating the interaction between stearidonic acid and its target molecules and receptors (ALOX5, COX-2, NF-kB and PPAR-γ). In all cancer cell lines (but not in the normal one), dose-dependent cytotoxic effects were observed after exposure to different concentrations of non-polar Tolypothrix extracts. The most pronounced inhibitory effect was observed on the HT-29 cell line, with an IC50 value of 106.27 µg/mL. A dose-dependent antioxidant effect was established for all tested extracts, measured by both DPPH and ABTS methods. All non-polar extracts reduced the production of pro-inflammatory cytokines IL-6 and TNF-α in LPS-stimulated macrophages RAW264.7, and the effects were dose-dependent. Analysis of the fatty acid composition revealed 26 different fatty acids. Our conclusion is that the Tolypothrix strains exhibit anticancer, antioxidant, and anti-inflammatory activity and could be a promising source for the production of natural products.

Oxylipins are bioactive lipids involved in inflammation. This study evaluated how a 2-week anti-inflammatory diet (ITIS, omega-3/omega-6 ratio of 1:1.5) affects plasma oxylipin profiles in patients with active Rheumatoid Arthritis (RA).

In an open-label pilot trial, 20 RA patients (≥3 tender and ≥3 swollen joints) followed the ITIS diet. Targeted lipidomics by mass spectrometry was used to quantify oxylipins. Patients were classified as responders or non-responders based on ≥50 % pain reduction (Pain-50). Dietary intake was assessed through diet scores, and statistical analyses were performed using RStudio.

Participants were predominantly female (90 %) with an average age of 57.1. At baseline, responders consumed more walnuts (p = 0.08), almond milk (p = 0.06), avocado (p = 0.04), and quinoa (p = 0.05), and fewer burgers (p = 0.02). No differences in diet adherence were observed between groups. Baseline oxylipin levels did not differ significantly. However, after the intervention, six oxylipins-5-HETE, 11,12-diHETrE, 14,15-diHETrE, 19,20-DiHDPA, 9-oxo-ODE, and 14,15-EET-differed significantly between responders and non-responders. Notably, oxylipins derived from both arachidonic acid (omega-6) and eicosapentaenoic acid (omega-3) decreased significantly after the diet (p = 0.0006 and p = 0.01, respectively).

The anti-inflammatory diet modified circulating levels of both pro- and anti-inflammatory oxylipins. These changes varied by pain response, suggesting that diet can influence inflammatory pathways in RA. Further studies are warranted to clarify the mechanisms linking dietary changes, oxylipin modulation, and clinical outcomes.

NCT04999683.

Inflammatory lung diseases (ILDs) represent a global public health crisis characterized by escalating prevalence, significant morbidity, and substantial mortality. In response to the complex immunopathogenic mechanisms driving these conditions, novel pharmacological strategies targeting resolution pathways have emerged throughout the discovery of specialized pro-resolving lipid mediator (SPM; resolvins, maresins, and protectins) dysregulation across the ILD spectra, positioning these endogenous molecules as promising therapeutic candidates for modulating maladaptive inflammation and promoting tissue repair. Over the past decade, this paradigm has catalyzed extensive translational research into SPM-based interventions as precision therapeutics for respiratory inflammation. In asthma, they reduce mucus hypersecretion, bronchial hyperreactivity, and airway inflammation, with prenatal SPM exposure potentially lowering offspring disease risk. In COPD, SPMs attenuate amyloid A-driven inflammation, normalizing cytokine/chemokine imbalances and oxidative stress and mitigating COVID-19-associated cytokine storm, enhancing survival. This review synthesizes SPMs' pharmacotherapeutic mechanisms in ILDs and evaluates current preclinical and clinical evidence.

Fish is the primary marine source that provides adequate nutrition to the human body. Fish production is increasing every year, contributing to a sustainable economy, as they provide a significant source of income and food: This review highlights the potential health benefits, industrial applications, and toxicity of various fish species Globally, fish possess various bioactive compounds; this efficacy makes them a more edible source to consume worldwide. A wide range of bioactive compounds, primary macronutrients, micronutrients, vitamins, and minerals are present in various fish types that are essential in preventing different human disorders. The nutritional value of fish helps to provide exceptional health benefits against different human ailments. Fish are excellent sources of protein, peptides, and polyunsaturated fatty acids, particularly eicosapentaenoic acid (EPA), Alpha-linolenic acid (ALA), omega-6 fatty acids, and docosahexaenoic acid (DHA), omega-3 fatty acids that influence human health positively. Fish and their by-products are also excellent sources for developing various nutraceutical and functional foods to fight against multiple human disorders. The by-products of fish exert significant effects against infection, viral attack, cardiovascular diseases, immune disorders, oxidative stress, inflammation, neurological diseases, and other physiological complications. Few fish species are contaminated with harmful substances that cause potential risks to children's and adults' bodies. Additionally, the therapeutic use of fish and their by-products unveils the potential nutritional benefits to reduce the burden on public health by managing dietary issues such as food security, protein deficiency, and other nutritional-related problems.

Women exhibit unique vulnerabilities in health, especially regarding mental health and neurodegenerative diseases. Biological, hormonal, and metabolic differences contribute to sex-specific risks that remain underrepresented in clinical studies. Diseases such as major depressive disorder (MDD) and Alzheimer's disease (AD) are more prevalent in women and may be influenced by hormonal transitions, particularly during menopause. Chronic low-grade inflammation is emerging as a shared mechanism underlying both conditions, and this inflammatory state can be worsened by dietary habits. During menopause, mood and sleep disturbances can influence dietary behavior, leading to enhanced snacking and consumption of high-glycemic and comfort foods. Such foods, low in nutritional value, promote weight gain and elevated inflammatory markers. Their consumption combined (or not) with a preexisting Western diet pattern-already linked to inflammation-could reinforce systemic inflammation involving the gut-brain axis. Moreover, the symptoms "per se" could act on inflammation as well. Peripheral inflammation may cross the blood-brain barrier, sustaining mood disorders and promoting neurodegenerative changes. Finally, MDD and AD are both associated with conditions such as obesity and diabetes, which occur more frequently in women. The review highlights how menopause-related changes in mood, sleep, and diet may heighten susceptibility to mental and neurodegenerative diseases.

Omega-3 fatty acids play a significant role in immunomodulation, with nutrigenomic approaches highlighting their impact on gene expression related to immune responses. Research indicates that omega-3 fatty acids can modulate inflammatory pathways, potentially reducing chronic inflammation and enhancing immune function. This review discusses the intersection of nutrigenomics and nutriepigenomics, focusing on how omega-3 fatty acids influence gene expression, immune function, and overall health. The immune system is a complex network responsible for defending the body against pathogens and maintaining internal balance. Comprised of innate and adaptive immunity, the system involves various cells, tissues, and organs working together to combat infections and prevent diseases. Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a significant role in modulating the immune system. These fatty acids influence immune cell function, membrane fluidity, and signaling processes, enhancing immune responses and reducing inflammation. Furthermore, EPA and DHA affect several signaling pathways, reducing the expression of proinflammatory cytokines and inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, a critical transcription factor in the inflammatory response. Additionally, they activate PPAR-γ, further diminishing inflammatory gene expression. As precursors to specialized proresolving lipid mediators, EPA and DHA help shift the lipid mediator profile from proinflammatory to antiinflammatory derivatives, thus aiding in the resolution of inflammation.

Delirium is a complex medical condition marked by acute episodes of cognitive dysfunction and behavioral disturbances, with a multifaceted etiology and challenging management across various clinical settings. Older adults, particularly in postoperative contexts, are at increased risk of developing delirium. Despite extensive research, a single underlying pathophysiological mechanism for delirium remains elusive. However, emerging evidence suggests a correlation between lipid dysregulation and delirium development in elderly patients, especially in postoperative settings. This connection has led to proposed treatments targeting dyslipidemia and associated neuroinflammatory effects in acute-phase delirium. This review aims to synthesize current literature on the relationship between lipid dysregulation and delirium in older adults, highlighting the need for further research into specific neurolipidome constituents and age-related lipid profile changes, potentially uncovering novel therapeutic strategies for delirium.

Long-term fasting (LF) activates an adaptative response to switch metabolic fuels from food glucose to lipids stored in adipose tissues. The increase in free fatty acid (FFA) oxidation during fasting triggers health benefits. We questioned if the changes in lipid metabolism during LF could affect lipids in cell membranes in humans. We thus analysed the FA composition in erythrocyte membranes (EM) during 12.6 ± 3.5 days of LF and 1 month after food reintroduction.

A total of 98 subjects out of three single-arm interventional studies underwent a medical supervised long-term fasting (12.6 ± 3.5 days) programme. The distribution pattern of 26 FA as well as the HS-Omega-3 Index were assessed in the EM using gas chromatography.

Eighteen of 26 FA showed significant changes. Within the group of saturated FA, myristic (14:0) and stearic acid (18:0) decreased while palmitic (16:0) and arachid acid (20:0) increased. While most monounsaturated FA increased, trans fatty acids decreased or remained unchanged. Within the polyunsaturated FA, arachidonic (20:4n6) and docosahexaenoic (22:6n3) acid increased, while linoleic (18:2n6), alpha-linolenic (18:3n3) and eicosapentaenoic acid (20:5n3) decreased. Consequently, the HS-Omega-3 Index increased. 11 out of the 18 FA with significant changes returned to baseline levels 1 month afterwards. Levels of linoleic and alpha-linolenic acid increased over baseline levels.

Long-term fasting triggers changes in the FA composition of EM.

Obesity is a significant global health issue, profoundly affecting metabolic and cardiovascular health and other related chronic conditions. In Chile, the prevalence of obesity is among the highest within the Organisation for Economic Cooperation and Development (OECD) countries, highlighting a critical public health challenge. This narrative review examines current evidence on the independent and potential synergistic roles of omega-3 fatty acids and exercise in managing obesity-related metabolic dysfunction. Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA), have been shown to lower triglyceride levels, enhance lipid metabolism, and modulate inflammation via pathways involving peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element-binding protein-1c (SREBP-1c). Exercise interventions, such as moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT), provide distinct yet complementary metabolic benefits. Specifically, MICT improves body fat distribution and mitochondrial efficiency, whereas HIIT has notable effects on metabolic adaptability and insulin signaling. Additionally, emerging evidence points toward a potential role of the kinin-kallikrein system, particularly kallikrein 7 (KLK7), in obesity-associated insulin resistance. Despite these promising findings, several knowledge gaps persist regarding optimal dosing, intervention timing, population-specific effects, and the exact mechanisms behind the potential synergistic interactions between omega-3 supplementation and structured exercise. This review emphasizes the importance of conducting further research, particularly controlled clinical trials, to clarify these combined interventions' effectiveness and establish targeted therapeutic strategies tailored to individual metabolic profiles.

Background: Orthopedic surgery and the corresponding events (i.e., immobilization and muscle disuse) result in a cascade of biological events to promote healing but can come with the loss of skeletal muscle mass and strength. A good nutritional status of patients is associated with positive post-surgical outcomes, with macronutrients receiving the majority of emphasis in the research literature. However, beyond the surgical literature, there are other nutrients and nutritional supplements that have been established or postulated to improve skeletal muscle mass and strength. Objective: The purpose of this narrative review is to provide evidence for the utility of using creatine, vitamin D, omega-3 fatty acids, glutamine, essential amino acids-branched chain amino acids (EAA-BCAA) and beta-hydroxy-beta-methylbutyrate (HMB) supplementation and the role they may play in minimizing muscle atrophy and strength loss following orthopedic surgery. The review will also highlight areas of future research to support a better understanding of the efficacy of supplementing with these substances pre- and/or post-surgery.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to help resolve inflammation through generation of anti-inflammatory eicosanoids and specialized pro-resolving mediators, including resolvins, protectins, and maresins. Through binding to the GPR120/FFAR4 receptor, their beneficial effects result from phospholipid membrane remodeling, impairment of inflammatory signaling molecules clustering, subsequent inhibition of NF-κB and inflammasome activation, and a reduction in oxidative stress. Obesity, a chronic inflammatory disease that contributes to metabolic disorders, is alleviated by n-3 PUFAs. In the adipose tissue (AT) of individuals with obesity, n-3 PUFAs counteract hypoxia, inhibit immune cell infiltration and AT inflammation, improve insulin sensitivity, and reduce fat mass. Beyond AT, n-3 PUFAs also alleviate other metabolic disorders such as metabolic-associated steatotic liver disease (MASLD), gut dysbiosis, and/or renal dysfunction. In cardiovascular disease (CVD), they are mainly recommended as a secondary prevention for patients with coronary heart disease risks. This review provides an in-depth analysis of the benefits of n-3 PUFAs in obesity and related metabolic diseases, examining both the mechanistic and clinical aspects. Additionally, it also explores the effects of n-3 PUFAs in obesity-related chronic inflammatory conditions, including inflammatory bowel disease, psoriasis, rheumatoid arthritis, osteoarthritis, and multiple sclerosis, by targeting specific pathophysiological mechanisms. Clinical applications and limitations of n-3 PUFAs are discussed based on findings from human clinical trials.

Selenium is an essential trace element for human health, but it mainly exists in an inorganic form that cannot be directly absorbed by the body. Brewer's yeast efficiently converts inorganic selenium into bioavailable organic selenium, making selenium-enriched yeast highly significant for human health research. Selenomethionine (SeM) is an important indicator for evaluating the quality of selenium-enriched yeast. Brewer's yeast was selected as the experimental subject, and the digestion of this yeast (Brewer's yeast) was simulated using an in vitro biomimetic gastrointestinal reactor to evaluate the effects of selenium-enriched yeast with various SeM levels on the gut flora of a healthy population. The experimental design comprised normal yeast (control group, OR), yeast containing moderate SeM levels (selenium-enriched group, SE), yeast containing high SeM levels (high-selenium group, MU), and a commercially available group comprising selenium-enriched yeast tablets (MA). The MU group exhibited a significantly higher concentration of short-chain fatty acids than the OR and MA groups during 48 h of fermentation, with significant differences observed (p < 0.05). Sequencing results revealed that the MU group showed significantly increased relative abundances of Bacteroidetes and Actinobacteria, while exhibiting a decreased ratio of Firmicutes to Bacteroidetes, which may simultaneously affect multiple metabolic pathways in vivo. These findings support the theory that selenium-enriched yeast with a high SeM has a more positive effect on human health compared with traditional yeast and offer new ideas for the development and application of selenium-enriched yeast.

Omega-3 (n-3) (e.g., EPA/DHA) and omega-6 (n-6) (e.g., linoleic acid [LA]) FAs are suggested to have opposite effects on inflammation, but results are inconsistent and direct comparisons of n-3 and n-6 are lacking. In a double-blind, randomized, and crossover study, females (n = 16) and males (n = 23) aged 30-70 years with abdominal obesity were supplemented with 3-4 g/d EPA/DHA (fish oil) or 15-20 g/d LA (safflower oil) for 7 weeks, with a 9-week washout phase. Cytokines and chemokines (multiplex assay), acute-phase proteins (MALDI-TOF mass spectrometry), endothelial function (vascular reaction index), blood pressure, FA composition (red blood cell membranes/serum/adipose tissue, GC-MS/MS), and adipose gene expression (microarrays, quantitative PCR) were measured. While significant differences between treatments in relative change scores were found for systolic blood pressure (n-3 vs. n-6: -1.81% vs. 2.61%, P = 0.003), no differences between n-3 and n-6 were found for any circulatory inflammatory markers. However, compared with baseline, n-3 was followed by reductions in circulating TNF (-24.9%, P < 0.001), regulated upon activation, normal T cell expressed and secreted (-12.1%, P < 0.001), and macrophage inflammatory protein 1-beta (-12.5%, P = 0.014), and n-6 by lowered TNF (-18.8%, P < 0.001), regulated upon activation, normal T cell expressed and secreted (-7.37%, P = 0.027), monocyte chemoattractant protein-1 (-7.81%, P = 0.020), and macrophage inflammatory protein 1-beta (-14.2%, P = 0.010). Adipose tissue showed significant treatment differences in weight percent of EPA (n-3 vs. n-6: 50.2%∗ vs. -1.38%, P < 0.001, ∗: significant within-treatment change score), DHA (16.0%∗ vs. -3.67%, P < 0.001), and LA (-0.033 vs. 4.91%∗, P < 0.001). Adipose transcriptomics revealed overall downregulation of genes related to inflammatory processes after n-3 and upregulation after n-6, partly correlating with changes in circulatory markers. These data point to tissue-specific proinflammatory effects of high n-6 intake, but a net systemic anti-inflammatory effect as for n-3.

Chronic kidney disease (CKD) is a condition caused by the gradual decline of renal function that approximatively affects 10-12% of the world population, thus representing a public health priority. In CKD patients, chronic and systemic low-grade inflammation is observed, and it significantly contributes to disease development and progression, especially for patients with advanced disease. It also results in CKD-associated complications and increased mortality. The low-grade inflammation is due to different factors, such as the decline of glomerular filtration rate, increased immune system activation, reactive oxygen species release, and intestinal homeostasis. Therefore, the possibility to control chronic low-grade inflammation in CKD deserves great attention. In this review, we will examine the current possible pharmacological approaches to counteract the inflammatory state in CKD, focusing our attention both on the pro-inflammatory factors and the pro-resolving mediators involved in CKD inflammatory state.

Background: Allergic asthma incidence is increasing, probably due to the influence of the Western diet. Adherence to the Mediterranean diet (MedDi) and omega-3 fatty acids composition (n-3 PUFAs) may be linked to a lower prevalence and lower severity of childhood asthma; however, the association is inconclusive. This study aims to examine the relationship between adherence to the MedDi, asthma severity, and erythrocyte fatty acid profile in Spanish children with atopic asthma. Methods: This study was based on an ongoing single-center, prospective, cross-sectional cohort study involving 95 consecutively enrolled children from an outpatient tertiary referral center. Of these, 55 had atopic asthma and 40 were age-matched healthy controls. Blood samples were collected to analyze the erythrocyte fatty acid content. Participants' demographic and clinical characteristics were recorded using validated self-reported outcome measures. Asthma severity and pulmonary function were assessed. Results: Asthmatics presented poorer adherence to the MedDi (p = 0.034) and lower n-3 PUFA levels (p = 0.019). Asthmatics with poor adherence to the MedDi were more likely to be overweight (p = 0.001) and to have moderate-severe asthma (p = 0.049); and lower n-3 PUFAs levels (p = 0.033). Children with mild asthma had higher n-3 PUFAs levels than those with moderate or severe asthma (p = 0.036). Conclusions: These findings highlight that adherence to the MedDi and a high erythrocyte fatty acid profile seem to have a protective effect in childhood asthma. Future well-controlled interventions should focus on the effects of MedDi patterns and n-3 PUFA intake on the primary prevention of childhood asthma.

Immunity is a fundamental aspect of animal biology, defined as the host's ability to detect and defend against harmful pathogens and toxic substances to preserve homeostasis. However, immune defenses are metabolically demanding, requiring the efficient allocation of limited resources to balance immune function with other physiological and developmental needs. To achieve this balance, organisms have evolved sophisticated signaling networks that enable precise, context-specific responses to internal and external cues. These networks are essential for survival and adaptation in multicellular systems. Central to this regulatory architecture is the STAT (signal transducer and activator of Transcription) family, a group of versatile signaling molecules that govern a wide array of biological processes across eukaryotes. STAT signaling demonstrates remarkable plasticity, from orchestrating host defense mechanisms to regulating dietary metabolism. Despite its critical role, the cell-specific and context-dependent nuances of STAT signaling remain incompletely understood, highlighting a significant gap in our understanding. This review delves into emerging perspectives on immunity, presenting dynamic frameworks to explore the complexity and adaptability of STAT signaling and the underlying logic driving cellular decision-making. It emphasizes how STAT pathways integrate diverse physiological processes, from immune responses to dietary regulation, ultimately supporting organismal balance and homeostasis.

Cardiovascular disease remains the leading global cause of mortality, largely driven by atherosclerosis, a chronic inflammatory condition characterized by lipid accumulation and immune-cell infiltration in arterial walls. Macrophages play a central role by forming foam cells and secreting pro-atherogenic cytokines, such as TNF-α, IFN-γ, and IL-1β, which destabilize atherosclerotic plaques, expanding the lipid core and increasing the risk of thrombosis and ischemia. Despite the significant health burden of subclinical atherosclerosis, few targeted therapies exist. Current treatments, including monoclonal antibodies, are limited by high costs and immunosuppressive side effects, underscoring the urgent need for alternative therapeutic strategies. In this study, we employed in silico drug repositioning to identify multitarget inhibitors against TNF-α, IFN-γ, and IL-1β, leveraging a virtual screening of 2750 FDA-approved drugs followed by molecular dynamics simulations to assess the stability of selected cytokine-ligand complexes. This computational approach provides structural insights into potential inhibitors. Additionally, we highlight nutraceutical options, such as fatty acids (oleic, linoleic and eicosapentaenoic acid), which exhibited strong and stable interactions with key cytokine targets. Our study suggests that these bioactive compounds could serve as effective new therapeutic approaches for atherosclerosis.

The potential of a plant-based diet (PD) to mitigate the adverse effects of long-term air pollution exposure on chronic obstructive pulmonary disease (COPD) remains uncertain. This study aims to explore both the independent and synergistic impacts of air pollution components and PD on COPD risk.

Annual concentrations of air pollutants, including particulate matter (PM2.5, PM2.5-10, and PM10), as well as nitrogen oxides (NOX) and nitrogen dioxide (NO2), were estimated using a land-use regression model. We calculated the plant-based diet index (PDI), healthy plant-based diet index (hPDI), and unhealthy plant-based diet index (uPDI) by evaluating scores of 17 food categories. Cox regression was performed to evaluate their individual and combined effects on COPD risk.

This prospective cohort study included 162,741 participants. Every standard deviation increase in PM2.5, NO2, and NOX exposure was associated with an increased risk of COPD, with an adjusted HR (95% CI) of 1.049 (1.019, 1.079), 1.065 (1.034, 1.096), and 1.063 (1.035, 1.092), respectively. Compared with low-quality hPDI, moderate- and high-quality hPDI were associated with a lower risk of COPD with an adjusted HR (95% CI) of 0.884 (0.827, 0.946) and 0.758 (0.697, 0.825), respectively. For the combined effects, with the level of hPDI increasing, the joint effects of hPDI with PM2.5, NO2, and NOX showed a gradually increasing negative impact on COPD risk (p-interaction = 0.001, 0.005, and 0.005, respectively).

Exposure to PM2.5, NO2, and NOx may elevate the risk of chronic obstructive pulmonary disease (COPD), whereas adherence to a high-quality hPDI could potentially counteract this association. Future research should explore the underlying biological mechanisms, assess the long-term effects of diet, and evaluate the effectiveness of dietary modifications in diverse populations to inform targeted prevention policies.

The MoKaRi study aims to evaluate the impact of two nutritional concepts on cardiometabolic risk factors.

For our 20-week intervention study, 65 participants with moderate elevated low-density lipoprotein cholesterol (LDL-C; ≥ 3 mmol/l) and without lipid-lowering therapy were recruited. The intervention to improve nutritional behavior was based on individualized menu plans which were characterized by defined energy and nutrient intake. To improve compliance, individual nutritional counselling sessions were held every two weeks. In addition to motivation, cooking skills were strengthened and nutritional knowledge was imparted. Follow-up visits were carried out after 10 and 20 weeks.

The MoKaRi diet lowered the concentrations of total cholesterol (menu plan group (MP): -15%; menu plan plus fish oil group (MP-FO): -11%), LDL-C (MP: -14%; MP-FO: -16%) and non-high-density lipoprotein cholesterol (MP: -16%; MP-FO: -13%) (p < 0.001). Body weight (MP: -5%; MP-FO: -8%; p < 0.05), waist circumference (MP: -6%; MP-FO: -9%) as well as diastolic blood pressure (MP: -8%; MP-FO: -8%), apolipoprotein A1 (MP: -15%; MP-FO: -20%), apolipoprotein B (MP: -15%; MP-FO: -6%) and glycated hemoglobin A1c (HbA1c) (MP: -1.8%; MP-FO: -3.6%) were also reduced in both groups after 20 weeks (p < 0.05). In both intervention groups, a maximum reduction in LDL-c of approx. 26% was achieved within the 20 weeks of intervention. Individual participants achieved a reduction of 45-49%. The supplementation of fish oil on top of the menu plans resulted in more substantial effects on body weight (MP: -5% vs. MP-FO: -8%), body fat (MP: -11% vs. MP-FO: -20%), triglycerides (MP: -14% vs. MP-FO: -28%), high-sensitivity C-reactive protein (MP: -19% vs. MP-FO: -43%) and HbA1c (MP: -1.8% vs. MP-FO:-3.6%; p < 0.05).

The MoKaRi diet resulted in a significant reduction of cardiometabolic risk factors. Our data highlights the additional benefit of the combination between menu plans and fish oil supplementation, which resulted in more substantial effects on body weight, BMI, TG, HbA1c and hs-CRP.

NCT02637778.

Discovery and translation of gene-environment interactions (GxEs) influencing clinical outcomes is limited by low statistical power and poor mechanistic understanding. Molecular omics data may help address these limitations, but their incorporation into GxE testing requires principled analytic approaches. We focused on genetic modification of the established mechanistic link between dietary long-chain omega-3 fatty acid (dN3FA) intake, plasma N3FA (pN3FA), and chronic inflammation as measured by high sensitivity CRP (hsCRP). We considered an approach that decomposes the overall genetic effect modification into components upstream and downstream of a molecular mediator to increase the potential to discover gene-N3FA interactions. Simulations demonstrated improved power of the upstream and downstream tests compared to the standard approach when the molecular mediator for many biologically plausible scenarios. The approach was applied in the UK Biobank (N = 188,700) with regression models that used measures of dN3FA (based on fish and fish oil intake), pN3FA (% of total fatty acids measured by nuclear magnetic resonance), and hsCRP. Mediation analysis showed that pN3FA fully mediated the dN3FA-hsCRP main effect relationship. Next, we separately tested modification of the dN3FA-hsCRP ("standard"), dN3FA-pN3FA ("upstream"), and pN3FA-hsCRP ("downstream") associations. The known FADS1-3 locus variant rs174535 reached p = 1.6 × 10-12 in the upstream discovery analysis, with no signal in the downstream analysis (p = 0.94). It would not have been prioritized based on a naïve analysis with dN3FA exposure and hsCRP outcome (p = 0.097), indicating the value of the decomposition approach. Gene-level enrichment testing of the genome-wide results further prioritized two genes from the downstream analysis, CBLL1 and MICA, with links to immune cell counts and function. In summary, a molecular mediator-focused interaction testing approach enhanced statistical power to identify GxEs while homing in on relevant sub-components of the dN3FA-hsCRP pathway.

Retrospective cohort study.

To understand how preoperative LDL levels, statin intake, and fish oil intake affect rates of pseudarthrosis after single-level and multilevel ACDF.

Anterior cervical discectomy and fusion (ACDF) is commonly performed to treat cervical degenerative diseases or injuries causing neck pain, myelopathy, and radiculopathy. Pseudarthrosis following ACDF can lead to persistent symptoms and may require revision surgery. No studies have explored the link between low-density lipoprotein (LDL) levels and statin or fish oil intake on pseudarthrosis in ACDF.

Patients undergoing ACDF were identified using TriNetX, a health care database with over 100 million patients. Pseudarthrosis rates following single-level and multilevel ACDF were compared between patients with high versus low LDL within one year before surgery. Pseudarthrosis rates were also compared between patients taking or not taking a statin as well as patients taking or not taking fish oil within six months before surgery. For all analyses, patients underwent propensity score matching in a 1:1 ratio based on relevant demographic factors and comorbidities.

Patients with an LDL above 142 mg/dL, compared with below 66 mg/dL, had significantly higher rates of pseudarthrosis at six months, one year, and two years after single-level and multilevel ACDF. Patients not taking a statin or fish oil, compared with those taking a statin or fish oil, respectively, also had significantly higher rates of pseudarthrosis at all time points after multilevel ACDF, but not single-level ACDF.

Low LDL levels are associated with reduced rates of pseudarthrosis after single-level and multilevel ACDF. Statin and fish oil intake before surgery are also associated with reduced rates of pseudarthrosis after multilevel, but not single-level ACDF. These associations may be used for preoperative planning, patient optimization, and risk stratification.

Age-related macular degeneration (AMD) is a leading cause of blindness in Western and developing countries. Since antivascular endothelial growth factor (VEGF) therapy is available for the regression of choroidal neovascularization (CNV), it does not work for the pathophysiology of AMD so a cure is increasingly demanded. Whale oil promotes various bodily functions, such as anti-inflammatory effects for cardiovascular disease, but its physiological mechanisms are still unclarified. Here, we examined the effects of whale oil on a mouse model of AMD. The area of CNV measured in choroidal flat-mount preparations at 7 days after laser photocoagulation was significantly smaller in mice fed whale oil compared with control mice free of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs). The plasma concentrations of ω-3 LCPUFAs were higher, whereas those of ω-6 LCPUFAs were lower in mice fed the diet containing whale oil than in those fed the control diet. The concentrations of various inflammatory cytokines and chemokines in the retina or choroid at 3 or 7 days after CNV induction differed between the two groups of mice. Furthermore, the concentration of VEGF was decreased in the retina but increased in the choroid at 7 or 3 days after photocoagulation, respectively. Our results thus show that dietary intake of whale oil-containing ω-3 LCPUFAs attenuated CNV in association with changes in inflammatory mediator levels and VEGF expression in the retina and choroid of mice, and it, therefore, warrants further study as a means to protect against AMD in humans.

Frequency of clinical cases of dogs with massive skin losses is very high in urban areas of Pakistan following road accidents, sharp objects exposure and attack by other dog. These cases need intensive veterinary assistance for safe and speedy healing of wounds. Recently, skin of Nile tilapia fish (Oreochromis niloticus) is internationally gaining hype in medical field as biological dressing to boost dermatological reconstruction process. Nile tilapia skin is a recent research trend and a very limited research data is available on this topic for both human and animal subjects. This study was conducted at Department of Small Animal Clinical Sciences, University of Veterinary and Animal Sciences (UVAS), Lahore, Pakistan considering the wound healing promoter properties of Nile tilapia skin as a biological dressing for dogs with massive skin losses. Aim of this study was to evaluate Nile tilapia fish skin as wound healing promoter biological dressing following sutured and non-sutured application techniques. For this study 10 clinical cases of dogs were randomly selected as per set criteria and divided into groups A and B comprising 5 dogs each. Consent document was signed by each dog owner for volunteer participation in this study. Nile tilapia skin was collected from fresh subjects and treated with 10% povidone-iodine for 10-15 minutes to prepare biological dressing. In group A, biological dressing was sutured on wound (non-absorbable silk suture material) on the area with dermal loss. In group B, biological dressing was applied in a wrap manner on area of dermal loss without application of sutures. Wound healing was evaluated grossly and histologically on days 0, 7 and 14. Statistical analysis of comparison between groups A and B revealed that application of Nile tilapia skin derived biological dressing in wrap fashion results in fast and complication-free wound healing as compared to sutured tilapia biological dressing in dogs.

The increasing prevalence of allergic rhinitis may be attributed to lifestyle changes such as dietary habits. Regarding dietary factors, n-3 and n-6 polyunsaturated fatty acids (PUFAs) are considered to be involved in the pathogenesis. Therefore, we examined whether the intake and serum concentrations of fatty acids affect inhaled allergen sensitization and the development of allergic rhinitis.

In total, 571 participants (20-69 years) from the Iwaki Health Promotion Project, a community-based project in 2022, were surveyed. Based on the results of PUFA intake and serum fatty acid concentrations obtained using a self-administered diet-history questionnaire, we examined whether n-3 or n-6 PUFAs were involved in reducing or increasing the risk of sensitization, respectively, and developing the disease. We also analyzed whether monounsaturated fatty acids-palmitoleic acid and oleic acid-were risk factors for sensitization and development. Univariate dietary intake, serum concentration, and logistic regression analyses were performed to identify the risk factors.

Our study revealed that higher serum concentrations of n-3 PUFAs were associated with a decreased risk of developing rhinitis, but had no effect on allergen sensitization in younger age group <50 years. Furthermore, palmitoleic acid had increased sensitization, and oleic acid may also increase the risk of the allergen sensitization.

n-3 PUFAs may reduce the risk of developing allergic rhinitis. Notably, palmitoleic acid may be a new risk factor that increases the risk of inhalant allergen sensitization and allergic rhinitis. These findings are significant in understanding the role of dietary factors in allergic rhinitis.

Butyrylcholinesterase (BChE; EC 3.1.1.8), a serine hydrolase found in various tissues, hydrolyses choline esters such as acetylcholine and succinylcholine, as well as other esters such as heroin and acetylsalicylic acid. It is considered to play a role in lipid metabolism as it belongs to the same enzyme group as lipases and its catalytic subunits are similar. In this study, the effects of unsaturated fatty acids, namely arachidonic (AA), linoleic (LA), alpha-linolenic (ALA) and oleic acid (OA), on equine serum BChE (EqBChE) were investigated. Enzyme activity was measured by the modified Ellman method. When the activity results were evaluated, the IC50 values were found 45.49, 8.465, 1556, and 56.57 μM; while the Ki values were 63.92, 11.46, 1800, and 15.24 μM for AA, ALA, LA, and OA, respectively. Analysis of the kinetic results showed that ALA was compatible with mixed inhibition and other fatty acids were compatible with non-competitive inhibition, a special type of mixed inhibition. Molecular docking predicted binding of the fatty acids to the active site, as well as to predicted allosteric sites. The results of this study provide another support to the hypothesis that cholinesterases are associated with lipid metabolism.

Polyunsaturated fatty acids (PUFAs) play a crucial role in aiding bacteria to adapt to extreme and stressful environments. While there is a well-established understanding of their production, accrual, and transfer within marine ecosystems, knowledge about terrestrial environments remains limited. Investigation of the intestinal microbiome of earthworms has illuminated the presence of PUFAs presumably of microbial origin, which contrasts with the surrounding soil. To comprehensively study this phenomenon, a multi-faceted approach was employed, combining fatty acid analysis with amplicon sequencing of the PfaA-KS domain of the anaerobic fatty acid synthase gene (pfa), as well as the 16S rRNA and 18S rRNA genes. This methodology was applied to scrutinize the gut microbiome of Eisenia fetida, its compost-based dietary source, and the resultant castings. This study unveiled a distinct gut soil ecosystem from input compost and output castings in fatty acid profile as well as type and abundance of organisms. 16S sequencing provided insights into the microbial composition, showing increased relative abundance of certain Pseudomonadota, including Shewanellaceae, and Planctomycetota, including Gemmataceae within the gut microbiome compared to input bulk soil compost, while Actinomycetota and Bacillota were relatively enriched compared to the casted feces. Sequencing of the PfaA-KS domain revealed amplicon sequence variants (ASVs) belonging primarily to Shewanella. Intriguingly, the 20C PUFAs were identified only in gut soil samples, though PfaA-KS sequence abundance was highest in output castings, indicating a unique metabolism occurring only in the gut. Overall, the results indicate that Shewanella can explain PUFA enrichment in the gut environment because of the pfa gene presence detected via PfaA-KS sequence data.IMPORTANCEPrior research has demonstrated that earthworm microbiomes can potentially harbor polyunsaturated fatty acids (PUFAs) that are not found within their residing soil environment. Moreover, distinct indicator species have been pinpointed for various microbial genera in earthworm microbiomes. Nevertheless, none of these studies have integrated metataxonomic and fatty acid analyses to explore the origin of PUFA synthesis in any earthworm species, with the objective of identifying the specific organisms and locations responsible for this production. This study suggests that earthworms accumulate PUFAs produced from bacteria, especially Shewanella, activated through the gut ecosystem.

Oxidative stress and inflammation are considered important risk contributors for various diseases. Over the last few decades, increasing attention has been focused on the role of n-3 polyunsaturated fatty acids (n-3 PUFAs) in human health and disease. We aimed to evaluate the effect of n-3 PUFA-enriched chicken meat consumption (~1500 mg of n-3 PUFAs intake per day) for three weeks on oxidative status and antioxidative capacity in young healthy individuals. This was a randomized, double-blinded, controlled trial, in which thirty-nine young healthy people were randomly allocated to eating 500 g/day of regular chicken meat (Control group) or n-3 PUFA-enriched chicken meat (n-3 PUFAs group) over 3 weeks. Subjects' biochemical parameters, including serum lipids level, liver enzymes, serum activities of antioxidant enzymes (glutathione peroxidase (GPx), superoxide dismutase (SOD)), serum oxidative stress markers (thiobarbituric acid reactive substances (TBARS) and ferric-reducing ability (FRAP)), as well as intracellular production of reactive oxygen species (ROS) in peripheral blood mononuclear cells, were assessed before and after completing the three-week dietary protocol. N-3-enriched chicken meat consumption significantly reduced high-sensitivity C reactive protein (hsCRP) serum level and increased the level of the antioxidant defense marker, FRAP. Furthermore, GPx and SOD enzyme activities significantly increased in the n-3 PUFAs group compared to baseline, which was accompanied by significantly decreased ROS production. In healthy young individuals, the 3-week dietary intake of n-3 PUFA-enriched chicken meat significantly increased the serum total antioxidant and anti-inflammatory potential, indicating that n-3 PUFAs may be protective in resting health condition without inflammatory processes.

Reduced docosahexaenoic acid (DHA) concentrations seem to be associated with an increased risk of Alzheimer's disease (AD), and DHA accretion to the brain across the blood-brain-barrier (BBB) can be modulated by various factors. Therefore, there is an urgent need to identify an efficient and non-invasive method to ensure brain DHA enrichment. In the present study, a safe and stable DHA-enriched nanoemulsion, designed to protect DHA against oxidation, was designed and administered intranasally in a transgenic mouse model of AD, the J20 mice. Intranasal treatment with nanoformulated DHA significantly improved well-being and working spatial memory in six-months-old J20 mice. These behavioral effects were associated with a reduction of amyloid deposition, oxidative stress, and neuroinflammation in brain tissues, which may be partially due to DHA-induced inactivation of the pleiotropic kinase GSK3β. In conclusion, intranasal DHA administration exhibited strong therapeutic effects and disease-modifying benefits in the J20 AD model. Given that DHA has already shown safety and tolerability in healthy human subjects, our results further support the need for clinical trials to assess the potential of this approach in Alzheimer's patients.