• arachidonic acid cascade
• fatty acids
• inflammation
• lipid mediators
• oxylipins

• Humans
• Docosahexaenoic Acids/pharmacology
• Macrophages/drug effects
• Macrophages/metabolism
• Dinoprostone/metabolism
• Dietary Supplements
• Fatty Acids, Omega-3/pharmacology
• Oxylipins/pharmacology
• Cells, Cultured
• Male
• Lipopolysaccharides/pharmacology
• Female
• Adult
• Cytokines/metabolism

• SCHE 1801 Deutsche Forschungsgemeinschaft (DFG)
• PhD fellowship
• Friedrich-Ebert-Stiftung

• Human adipose tissue
• Marine-source omega-3 fatty acids
• NLRP3 inflammasome and interleukin-1 beta
• Plasma apoB
• Type 2 diabetes

• Adult
• Female
• Humans
• Male
• Middle Aged
• Adipose Tissue/metabolism
• Adipose Tissue/drug effects
• Adipose Tissue, White/metabolism
• Adipose Tissue, White/drug effects
• Diabetes Mellitus, Type 2/metabolism
• Docosahexaenoic Acids/pharmacology
• Eicosapentaenoic Acid/pharmacology
• Inflammasomes/metabolism
• Interleukin-1beta/metabolism
• Lipoproteins, LDL/metabolism
• Lipoproteins, LDL/blood
• NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
• Risk Factors
• Signal Transduction/drug effects
• Up-Regulation/drug effects

• #123409 Canadian Institute of Health Research

• COPD
• HMB
• Metabolism
• PUFA
• RCT
• Stable isotopes

• Humans
• Pulmonary Disease, Chronic Obstructive/drug therapy
• Valerates/administration & dosage
• Valerates/pharmacology
• Dietary Supplements
• Male
• Female
• Double-Blind Method
• Aged
• Middle Aged
• Fatty Acids, Omega-3/administration & dosage
• Fatty Acids, Omega-3/pharmacology
• Quality of Life
• Eicosapentaenoic Acid/administration & dosage
• Eicosapentaenoic Acid/pharmacology
• Docosahexaenoic Acids/administration & dosage

• Fat
• Inflammation
• Lipids
• Lipopolysaccharide
• Taste buds

• Animals
• Mice
• Endotoxemia/chemically induced
• Interleukin-6/genetics
• Lipopolysaccharides/toxicity
• Tumor Necrosis Factor-alpha
• Anti-Inflammatory Agents/pharmacology
• Anti-Inflammatory Agents/therapeutic use
• Inflammation
• CD36 Antigens/genetics
• Cytokines/genetics
• Interleukin-1beta/genetics
• RNA, Messenger
• Fatty Acids

• A dose–response meta-analysis
• Cancer cachexia
• Omega-3
• Weight gain

• Humans
• Aged
• Cachexia/drug therapy
• Cachexia/complications
• Randomized Controlled Trials as Topic
• Body Weight
• Dietary Supplements/adverse effects
• Neoplasms/complications

• Blue economy
• Dried blood spot
• Fatty acid ethyl esters
• Lipidomics
• Tuna fish industry
• Waste valorization

• Animals
• Humans
• Esters
• Gas Chromatography-Mass Spectrometry
• Fatty Acids, Omega-3
• Eicosapentaenoic Acid
• Fatty Acids
• Dietary Supplements

• Association
• CRC
• Colon cancer
• Meta-analysis
• Rectal cancer
• Trans fatty acid

• Walnut oil
• chemistry
• extraction
• health benefits
• medicinal value

• Body weight
• Cancer cachexia
• Meta-analysis
• Survival
• n-3 polyunsaturated fatty acids

• Blimp1
• Effector CD4(+) T cells
• Glycolysis
• Inflammatory Bowel Diseases
• Intestinal Homeostasis

• Acetates/pharmacology
• Adoptive Transfer
• Animals
• Anti-Inflammatory Agents, Non-Steroidal/pharmacology
• CD4-Positive T-Lymphocytes/drug effects
• CD4-Positive T-Lymphocytes/immunology
• CD4-Positive T-Lymphocytes/metabolism
• CD4-Positive T-Lymphocytes/transplantation
• Case-Control Studies
• Colitis/immunology
• Colitis/metabolism
• Colitis/prevention & control
• Colitis, Ulcerative/immunology
• Colitis, Ulcerative/metabolism
• Colon/drug effects
• Colon/immunology
• Colon/metabolism
• Crohn Disease/immunology
• Crohn Disease/metabolism
• Disease Models, Animal
• Glycolysis/drug effects
• Interleukin-10/genetics
• Interleukin-10/metabolism
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, G-Protein-Coupled/agonists
• Receptors, G-Protein-Coupled/genetics
• Receptors, G-Protein-Coupled/metabolism
• Signal Transduction
• Tyramine/analogs & derivatives
• Tyramine/pharmacology
• Mice

• R01 DK124132 NIDDK NIH HHS
• R01 DK125011 NIDDK NIH HHS
• R21 AI150210 NIAID NIH HHS

• gastrointestinal diseases
• healthy aging
• malnutrition

• Aged
• Aged, 80 and over
• Elder Nutritional Physiological Phenomena
• Female
• Gastrointestinal Diseases/complications
• Gastrointestinal Diseases/prevention & control
• Gastrointestinal Diseases/therapy
• Geriatric Assessment
• Healthy Aging
• Humans
• Male
• Malnutrition/epidemiology
• Malnutrition/prevention & control
• Malnutrition/therapy
• Nutrition Assessment
• Nutrition Therapy
• Quality of Life

Inflammation is one of the primary factors associated with the causation and/or progression of several lifestyle disorders, including obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). NAFLD is a spectrum of disorders, and starts with simple steatosis, progresses to non-alcoholic steatohepatitis, and then advances to fibrosis, cirrhosis and finally, hepatocellular carcinoma, due to perpetual cycles of insults caused by inflammation and other cellular stress. Emerging evidence has documented that patients with NAFLD have severe coronavirus disease 2019 (COVID-19), and patients with COVID-19 have a higher liver injury and mortality. Although the exact cause or mechanism is not known, inflammatory cytokine storm is a characteristic feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is known to be associated with higher mortality among COVID-19 patients. Therefore, the COVID-19 pandemic seems to be a major concern in NAFLD patients, who have contracted SARS-CoV-2 infection and develop COVID-19. This is evident in patients at any stage of the NAFLD spectrum, as the inflammatory cytokine storm may cause and/or aggravate the progression or severity of NAFLD. Thus, there is a need for resolution of the inflammatory cytokine storm in these patients. A large body of evidence has demonstrated the efficacy of omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) in NAFLD conditions, due to their anti-inflammatory, immunomodulatory and anti-viral properties. Therefore, intervention with ω-3 LCPUFA, an effective pharmaconutrient along with the standard treatment for COVID-19 may be useful in the management of the NAFLD spectrum in COVID-19 patients with pre-existing NAFLD conditions by resolving the inflammatory cytokine storm and thereby attenuating its progression. Although there are challenges in implementation, optimistically they can be circumvented and the pharmaconutrition strategy may be potentially helpful in tackling both the pandemics; NAFLD and COVID-19 at least in this subset of patients.

• Lipids
• Virus
• Inflammation
• Infection
• Fish oil
• Supplementation

• Anxiety
• Depression
• Docosahexaenoic acid
• Eicosapentaenoic acid
• Stress

• Adolescent
• Adult
• Anxiety/drug therapy
• Depression/drug therapy
• Dietary Supplements
• Docosahexaenoic Acids/therapeutic use
• Double-Blind Method
• Eicosapentaenoic Acid/therapeutic use
• Female
• Humans
• Magnesium/therapeutic use
• Male
• Patient Health Questionnaire
• Randomized Controlled Trials as Topic
• Stress, Psychological/drug therapy
• Vitamin E/therapeutic use
• Young Adult

• dietary regimens
• macronutrients
• micronutrients
• minerals
• nerve injury
• peripheral nervous system
• vitamins

• Clinical randomized trial
• Lipid emulsion
• Meta-analysis
• SMOFlipid
• ω-3 polyunsaturated fatty acids

• Polyporus umbellatus
• chronic renal failure
• ergone
• fatty acid metabolism
• lipidomics
• mass spectrometry
• ultra-performance liquid chromatography

• DHA
• EPA
• Inflammation
• Monocytes
• Randomized crossover trial
• Specialized pro-resolving lipid mediators

• Cross-Over Studies
• Dietary Supplements
• Docosahexaenoic Acids
• Double-Blind Method
• Eicosapentaenoic Acid
• Fatty Acids, Omega-3
• Female
• Humans
• Inflammation
• Male
• Monocytes

Cancer cachexia is a complex metabolic syndrome characterized by involuntary skeletal muscle loss and is associated with poor clinical outcome, decreased survival and negatively influences cancer therapy. No curative treatments are available for cancer cachexia, but nutritional intervention is recommended as a cornerstone of multimodal therapy. Optimal nutritional care is pivotal in the treatment of cancer cachexia, and the effects of nutrients may extend beyond provision of adequate energy uptake, targeting different mechanisms or metabolic pathways that are affected or deregulated by cachexia. The evidence to support this notion derived from nutritional intervention studies in experimental models of cancer cachexia is systematically discussed in this review. Moreover, experimental variables and readout parameters to determine skeletal muscle wasting and cachexia are methodologically evaluated to allow critical comparison of similar studies. Single- and multinutrient intervention studies including qualitative modulation of dietary protein, dietary fat, and supplementation with specific nutrients, such as carnitine and creatine, were reviewed for their efficacy to counteract muscle mass loss and its underlying mechanisms in experimental cancer cachexia. Numerous studies showed favorable effects on impaired protein turnover and related metabolic abnormalities of nutritional supplementation in parallel with a beneficial impact on cancer-induced muscle wasting. The combination of high quality nutrients in a multitargeted, multinutrient approach appears specifically promising, preferentially as a multimodal intervention, although more studies investigating the optimal quantity and combination of nutrients are needed. During the review process, a wide variation in timing, duration, dosing, and route of supplementation, as well as a wide variation in animal models were observed. Better standardization in dietary design, and the development of experimental models that better recapitulate the etiology of human cachexia, will further facilitate successful translation of experimentally-based multinutrient, multimodal interventions into clinical practice.

• cachexia
• cancer
• multimodal
• multinutrient
• multitarget
• nutrition
• undernutrition

• cytokines
• fatty acids
• macronutrients
• non-alcoholic fatty liver disease (NAFLD)

• Animals
• Diet, High-Fat/adverse effects
• Fatty Acids, Omega-3/administration & dosage
• Fatty Acids, Omega-3/chemistry
• Fatty Acids, Omega-6/administration & dosage
• Fatty Acids, Omega-6/chemistry
• Fatty Liver/chemically induced
• Fatty Liver/pathology
• Gene Expression Regulation/drug effects
• Inflammation/chemically induced
• Liver/metabolism
• Male
• Mice
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Rapeseed Oil/chemistry
• Rapeseed Oil/pharmacology
• Soybean Oil/chemistry
• Soybean Oil/pharmacology

• 249/2013 Nucleus of Excellence Support Program
• 88882.448882/2019-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
• 2018/09868-7 Fundação de Amparo à Pesquisa do Estado de São Paulo

• Juglans sigillata
• anti-oxidant
• gut microbiota
• intestinal mucosa
• operational taxonomic units (OTUs)
• secretory immunoglobulin A (S-IgA)
• tumor necrosis factor-α (TNF-α)
• walnut oil

Polyunsaturated fatty acids of the n-3 series (n-3 PUFA) exhibit a number of favorable effects on the human organism and it is desirable to increase their intake in the diet. For this purpose, flaxseed oil was added to a chicken-feed mixture for the production of meat and eggs. The content of n-3 PUFA in the obtained meat was increased from 250 mg (reference value) to 900 mg in 100 g of meat and from 110 mg (reference value) to 190 mg in 100 g of whole egg; the enriched products are designated as omega-3 meat and omega-3 eggs. Omega-3 meat and eggs were subsequently fed for a period of eight weeks in an amount of 480 g of meat and four eggs (228 g netto) a week to a group of 14 healthy volunteers, whose body composition parameters were measured and blood was analyzed biochemically to determine blood lipids, coagulation parameters, plasma, and erythrocyte fatty acid spectrum composition. A control group of 14 volunteers was fed normal chicken and eggs in the same regime. The performed dietary intervention increases the intake of long-chain PUFA (LC-PUFA) by 37 mg per day, which represents 7–15% of the recommended daily dose. The performed tests demonstrated that the consumption of omega-3 enriched meat and eggs significantly increases the content of n-3 PUFA in the erythrocytes, which are a long-term indicator of fatty acid intake. This intervention has no demonstrable effect on the basic body parameters, such as body weight, fat content, Body Mass Index (BMI), and also on the plasma cholesterol level, high-density lipoprotein (HDL), low-density lipoprotein (LDL), blood clotting and inflammation markers, and omega-3 index.

• blood coagulation
• blood lipids
• body composition
• erythrocytes
• fatty acids spectrum
• n-3 polyunsaturated fatty acids
• omega-3 diet

• Adolescent
• Adult
• Body Mass Index
• Cardiovascular Diseases/prevention & control
• Diet/methods
• Eggs
• Erythrocytes/chemistry
• Fatty Acids/blood
• Fatty Acids, Omega-3/administration & dosage
• Food, Fortified
• Healthy Volunteers
• Heart Disease Risk Factors
• Humans
• Lipoproteins, HDL/blood
• Lipoproteins, LDL/blood
• Male
• Meat
• Single-Blind Method
• Young Adult

The consumption of docosahexaenoic acid (DHA) has beneficial effects on human health. Meat from suckling goat kids is highly valuable, especially in Mediterranean countries. Based on this, several strategies have been implemented to increase the content of DHA in foodstuffs such as meat and meat products. Several studies have observed how feeding diverse sources of DHA can improve the fatty acid profile in goat kid meat. However, few studies have focused on the effect of using these DHA supplements on growth and the immune system development in these animals. Consequently, this study aimed to evaluate the effect of different levels of DHA supplementation on growth and the immune system development in newborn goat kids. The current study showed that the DHA supplementation did not affect either growth or the immune status of goat kids during the first 35 days of life.

Consumption of polyunsaturated fatty acids (PUFA), especially docosahexaenoic acid (DHA), has beneficial effects for consumers’ health. Consequently, there is an increased interest in enhancing meat fatty acid profiles (i.e., PUFA and DHA content) through diverse nutritional strategies. This study aimed to investigate the effect of supplementing a microalgae-derived product rich in DHA on growth and immune system development in newborn goat kids. In this experiment, newborn goat kids were fed milk replacer (MR) supplemented with three levels of a microalgae-derived product rich in DHA (DHA-Gold^®, Martek Biosciences, MD, USA). Groups were designed as follows: MR-NS (milk replacer without DHA-Gold^® supplementation; n = 10), MR-DHA-9 (9 g of DHA-Gold^®/L milk replacer; n = 10) and MR-DHA-18 (18 g of DHA-Gold^®/L milk replacer; n = 10). The immune status of the kids was evaluated by the plasma IgG and IgM concentrations, as well as by the complement system and chitotriosidase activities. Dietary supplementation with DHA did not affect either growth or innate and humoral immunity (p > 0.05). This study concludes that supplementation with DHA does not cause negative effects on growth and immune status in newborn goat kids.

• DHA
• chitotriosidase
• complement activity
• goat kid
• meat quality
• omega-3

• colon cancer surgery
• cytokines
• immune response
• intravenous omega-3 fatty acids
• postoperative complications

• FADS
• desaturation
• disease
• fatty acid desaturase
• polyunsaturated fatty acid

• Fatty Acid Desaturases/genetics
• Fatty Acid Desaturases/metabolism
• Fatty Acids, Unsaturated/metabolism
• Humans
• Plants/enzymology

• NCN 2016/22/E/NZ4/00665 Narodowe Centrum Nauki
• POWR.03.02.00-00-I026/17-00 European Union through the European Social Fund under the Operational Programme Knowledge Education Development

This trial addresses the global problem of chronic venous leg ulcers (CVLUs), wounds that cause significant infirmity for an estimated 9.7 million people annually, mainly older adults with comorbidities. Advanced therapies are needed because standard topical therapies are often ineffective or yield only short-term wound healing. Thus, we are testing a new oral therapy containing the bioactive elements of fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for targeting and reducing the high numbers of activated polymorphonuclear leukocytes (PMN) in wound microenvironments that keep CVLUs “trapped” in a chronic inflammatory state.

This double-blind RCT will include 248 eligible adults ≥ 55 years of age with CVLUs receiving standard care at a large Midwest outpatient wound clinic. Participants are randomized to two groups: 12 weeks of daily oral therapy with EPA + DHA (1.87 g/day of EPA + 1.0 g/day of DHA) or daily oral therapy with placebo. At 0, 4, 8, and 12 weeks, across the two groups, we are pursuing three specific aims: Aim 1. Compare levels of EPA + DHA-derived lipid mediators, and inflammatory cytokines in blood and wound fluid; Subaim 1a. Compare inflammatory cytokine gene expression by PMNs in blood; Aim 2. Compare PMN activation in blood and wound fluid, and PMN-derived protease levels in wound fluid; Aim 3. Compare reduction in wound area, controlling for factors known to impact healing, and determine relationships with lipid mediators, cytokines, and PMN activation. Subaim 3a. Compare frequency of CVLU recurrence and levels of study variables in blood between the randomly assigned two subgroups (continuing EPA + DHA therapy versus placebo therapy beyond week 12) within the EPA + DHA group with healed CVLUs after 3 months of therapy. Subaim 3b. Compare symptoms of pain at all time points and quality of life at first and last time points across the two groups and two subgroups.

This trial will provide new evidence about the effectiveness of EPA + DHA oral therapy to target and reduce excessive PMN activation systemically and locally in patients with CVLUs. If effective, this therapy may facilitate healing and thus be a new adjunct treatment for CVLUs in the aging population.

ClinicalTrials.gov, NCT03576989; Registered on 13 June 2018.

• Fatty acids
• Fish Oil
• Inflammation
• Polymorphonuclear leukocytes
• Venous leg ulcers

• Salmonella
• mechanism
• n-3 LCPUFAs
• prevention

• Animals
• Bacteria/classification
• Bacteria/genetics
• Bacteria/isolation & purification
• Bacteria/metabolism
• Dietary Supplements/analysis
• Disease Models, Animal
• Fatty Acids, Omega-3/administration & dosage
• Fatty Acids, Volatile/metabolism
• Female
• Gastrointestinal Microbiome/drug effects
• Humans
• Mice
• Mice, Inbred C57BL
• Salmonella/drug effects
• Salmonella/physiology
• Salmonella Infections/microbiology
• Salmonella Infections/prevention & control

• QoL
• bortezomib
• chemotherapy-induced peripheral neuropathy
• multiple myeloma
• nutraceutical compound
• prevention

Background: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca²⁺ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). Methods: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca²⁺ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. Results: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca²⁺ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. Conclusion: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.

• PTHrP
• cachexia
• fish oil
• hypercalcemia
• leucine

Lipid metabolism imbalance has been recognized as one of the major drivers of impaired glucose metabolism in the context of type 2 diabetes mellitus (T2DM), the rates of which are steadily increasing worldwide. Impaired glucose regulation (IGR) plays a vital role in the prevention and treatment of T2DM. The goal of this study was to further clarify whether the combination of plant sterols (PS) and omega-3 fatty acids yields any synergistic effect that enhances the prevention and treatment of IGR.

A total of 200 participants were randomized to receive PS and omega-3 fatty acids (n = 50), PS alone (n = 50), omega-3 fatty acids alone (n = 50), or placebo soy bean powder plus placebo capsules (n = 50) for 12 weeks. Patient characteristics including body composition, blood pressure, glucose metabolism (Fasting plasma glucose (FPG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)), lipid metabolism (TG, TC, HDL-C, LDL-C) and inflammatory factors (Hs-CRP, IL-6) were all monitored in these IGR individuals.

Compared to the placebo group, the group receiving the combined intervention exhibited significantly decreased TG, HDL-C, FBG, HOMA-IR and HbA1c. Omega-3 fatty acids alone were associated with significant reductions in waistline, TG, FBG, HOMA-IR and Hs-CRP. PS alone was only associated with decreased TG and Hs-CRP. No interventions produced significant changes in body weight, BMI, blood pressure, FINS, body fat percentage, visceral fat rating, TC, LDL-C or IL-6.

In summary, this study has demonstrated for the first time that PS, omega-3 fatty acids or the combination thereof significantly improved inflammation, insulin resistance, as well as glucose and lipid metabolism in IGR individuals. These findings may provide a scientific basis for the development of nutritional products incorporating PS and omega-3 fatty acids, and also for the development of nutritional supplement strategies aimed at preventing the development of disease in the IGR population.

• Factorial design
• Impaired glucose regulation
• Omega-3 fatty acids
• Plant sterols

Respiratory infections challenge the swine industry, despite common medicinal practices. The dual signaling nature of PGE₂ (supporting both inflammation and resolution) makes it a potent regulator of immune cell function. Therefore, the use of dietary long chain n-6 PUFA to enhance PGE₂ effects merits investigation.

Day-old pigs (n = 60) were allotted to one of three dietary groups for 21 d (n = 20/diet), and received either a control diet (CON, arachidonate = 0.5% of total fatty acids), an arachidonate (ARA)-enriched diet (LC n-6, ARA = 2.2%), or an eicosapentaenoic (EPA)-enriched diet (LC n-3, EPA = 3.0%). Alveolar macrophages and lung parenchymal tissue were collected for fatty acid analysis. Isolated alveolar macrophages were stimulated with LPS in situ for 24 h, and mRNA was isolated to assess markers associated with inflammation and eicosanoid production. Culture media were collected to assess PGE₂ secretion. Oxidative burst in macrophages was measured by: 1) oxygen consumption and extracellular acidification (via Seahorse), 2) cytoplasmic oxidation and 3) nitric oxide production following 4, 18, and 24 h of LPS stimulation.

Concentration of ARA (% of fatty acids, w/w) in macrophages from pigs fed LC n-6 was 86% higher than CON and 18% lower in pigs fed LC n-3 (P < 0.01). Following LPS stimulation, abundance of COX-2 and TNF-α mRNA (P <  0.0001), and PGE₂ secretion (P < 0. 01) were higher in LC n-6 PAM vs. CON. However, ALOX5 abundance was 1.6-fold lower than CON. Macrophages from CON and LC n-6 groups were 4-fold higher in ALOX12/15 abundance (P < 0.0001) compared to LC n-3. Oxygen consumption and extracellular acidification rates increased over 4 h following LPS stimulation (P < 0.05) regardless of treatment. Similarly, increases in cytoplasmic oxidation (P < 0.001) and nitric oxide production (P <  0.002) were observed after 18 h of LPS stimulation but were unaffected by diet.

We infer that enriching diets with arachidonic acid may be an effective means to enhance a stronger innate immunologic response to respiratory challenges in neonatal pigs. However, further work is needed to examine long-term safety, clinical efficacy and economic viability.

The online version of this article (10.1186/s40104-019-0321-1) contains supplementary material, which is available to authorized users.

• Arachidonic acid
• Cyclooxygenase
• Eicosanoid
• Eicosapentaenoic acid
• Inflammation
• LPS
• Lipid mediator class switch
• Lipoxin
• Porcine alveolar macrophage

• overweight and obese adult men and postmenopausal women
• δ-5-desaturase
• δ-6-desaturase
• plasma phospholipid fatty acids
• apob-lipoproteins
• atherogenic dyslipidemia
• postprandial fat metabolism
• insulin resistance
• interleukin-1
• type 2 diabetes

• Adipose
• Inflammation
• Lipid
• Obesity
• Omega-3 fatty acid

Background and Aims: Peripheral neuropathy is a common complication of chemotherapy that can induce marked disability that negatively affects the quality of life in patients with multiple myeloma (MM). The aim of this study was to prevent the onset or the worsening of peripheral neuropathy in MM patients treated with bortezomib (BTZ), using a new nutritional neuroprotective compound. We report preliminary results of 18 out of 33 patients who completed the study. Methods: We administered a tablet of Neuronorm to patients, containing docosahexaenoic acid 400 mg, α-lipoic acid 600 mg, vitamin C 60 mg, and vitamin E 10 mg bid for the whole follow-up period. Neurological visit assessment, electroneurography, and evaluation scales were performed at baseline and after 6 months. Results: At 6 months, 8 patients had no chemotherapy-induced peripheral neuropathy, while 10 patients experienced chemotherapy-induced peripheral neuropathy of grade 1 according to the Common Terminology Criteria for Adverse Events, one of them with pain. Seventeen patients did not report painful symptoms; no limitation of functional autonomy and stability in quality of life domains explored was observed. Conclusions: Our results seem to indicate that early introduction of a neuroprotective agent in our patients with MM treated with BTZ could prevent the onset or the worsening of neuropathic pain, avoiding the interruption of the therapy with BTZ, and maintaining a good functional autonomy to allow normal daily activities. Despite the limitations due to the fact that this is a preliminary study, in a small population, with short follow-up, our data seem to indicate that the nutraceutical may have some potential to be considered for a future trial.

• ALA
• DHA
• bortezomib
• docosahexaenoic acid
• multiple myeloma
• peripheral neuropathy
• peripheral neuropathy assessment
• α-lipoic acid

• Administration, Oral
• Aged
• Aged, 80 and over
• Aging/blood
• Aging/immunology
• Aging/pathology
• Chronic Disease
• Dietary Supplements
• Docosahexaenoic Acids/administration & dosage
• Docosahexaenoic Acids/blood
• Double-Blind Method
• Drug Administration Schedule
• Eicosapentaenoic Acid/administration & dosage
• Eicosapentaenoic Acid/blood
• Female
• Humans
• Interleukin-1beta/antagonists & inhibitors
• Interleukin-1beta/blood
• Interleukin-1beta/immunology
• Interleukin-6/antagonists & inhibitors
• Interleukin-6/blood
• Interleukin-6/immunology
• Male
• Middle Aged
• Tumor Necrosis Factor-alpha/antagonists & inhibitors
• Tumor Necrosis Factor-alpha/blood
• Tumor Necrosis Factor-alpha/immunology
• Varicose Ulcer/blood
• Varicose Ulcer/diet therapy
• Varicose Ulcer/immunology
• Varicose Ulcer/pathology

• R21 NR012803 NINR NIH HHS

• n-3 PUFA
• n-3 PUFA n-3 PUFA
• ECAR extracellular acidification rate
• FO fish oil
• GP generalised polarisation
• GPMV giant plasma membrane vesicle
• LA linoleic acid
• OCR VO2 rate
• OO olive oil
• UT untreated
• CD4+ T cells
• Generalised polarisation
• Giant plasma membrane vesicles
• Phase separation

• Docosahexaenoic acid
• Folate
• Inflammation
• Pregnancy induced hypertension
• Vitamin B(12)

Present study aimed to better understand the potential apoptotic pathways that involved in docosahexaenoic acid (DHA)-induced apoptosis of prostate cancer cells.

Human prostate cancer DU145 cells were treated with different concentrations of fish oil, omega-3 PUFA (DHA, and Eicosapentaenoic acid, EPA), or omega-6 PUFA (Arachidonic acid, AA). Cell viability and apoptosis were evaluated by MTT assay and Hoechst staining. Pathway-focused gene expression profiling of DU145 cells was analyzed with the RT² Profile PCR Array System. The results were verified by real time quantitative polymerase chain reaction (RT-qPCR).

AA exposure showed no obvious effect on viability of DU145 cells. However, exposure with fish oil, EPA, or DHA for 24 h significantly affected cell viability. The growth inhibition of DHA was more pronounced than that of EPA and showed a time-dependent increase. DHA exposure caused typical apoptotic characteristics. Ten genes were more expressed, while 5 genes were less expressed following DHA exposure. RT-qPCR confirmed the time dependent effect of DHA on the expression of these differentially expressed genes. KEGG pathway analysis showed that DHA may induce the apoptosis of cancer cells preferentially through mediating P53, MAPK, TNF, PI3K/AKT, and NF-κB signaling pathways.

Our study demonstrated the beneficial action of DHA on human prostate carcinoma cell line DU145. The pro-apoptotic effect of DHA on DU145 cells may involve mediation various pathways, especially P53, MAPK, TNF, PI3K/AKT, and NF-κB signaling pathways. Molecular mechanisms of DHA on apoptosis of cancer cells still need to be further clarified.

The online version of this article (doi:10.1186/s12944-017-0442-5) contains supplementary material, which is available to authorized users.

• DU145 cells
• Docosahexaenoic acid (DHA)
• Human prostate carcinoma cell
• RT2 profile PCR array system

• Cancer
• Cancer therapy
• Ketogenic diet
• Ketone bodies
• Metabolism

• Inflammatory response
• angiogenesis
• biomaterials
• macrophages
• natural compounds.
• tissue engineering

• Biocompatible Materials/chemistry
• Biocompatible Materials/pharmacology
• Biological Products/chemistry
• Biological Products/pharmacology
• Humans
• Inflammation/drug therapy
• Tissue Engineering
• Wound Healing/drug effects

• P20 GM103641 NIGMS NIH HHS
• R03 AR063338 NIAMS NIH HHS

Since lipid compounds are known to modulate the function of CD4⁺ T-cells and macrophages, we hypothesize that altered levels of serum non-esterified fatty acids (NEFA) may underlie rheumatoid arthritis (RA) pathogenesis.

Serum levels of NEFA (palmitic, stearic, palmitoleic, oleic, linoleic, γ-linoleic, arachidonic –AA–, linolenic, eicosapentaenoic –EPA– and docosahexaenoic –DHA–) were quantified by LC-MS/MS after methyl-tert-butylether (MTBE)-extraction in 124 RA patients and 56 healthy controls (HC). CD4⁺ phenotype was studied by flow cytometry. TNFα, IL-8, VEGF, GM-CSF, IFNγ, IL-17, CCL2, CXCL10, leptin and resistin serum levels were quantified by immunoassays. The effect of FA on IFNγ production by PBMC was evaluated in vitro.

Lower levels of palmitic (p<0.0001), palmitoleic (p = 0.002), oleic (p = 0.010), arachidonic (p = 0.027), EPA (p<0.0001) and DHA (p<0.0001) were found in RA patients, some NEFA being altered at onset. Cluster analysis identified a NEFA profile (hallmarked by increased stearic and decreased EPA and DHA) overrepresented in RA patients compared to HC (p = 0.002), being associated with clinical features (RF, shared epitope and erosions), increased IFNγ expression in CD4⁺ T-cells (p = 0.002) and a Th1-enriched serum milieu (IFNγ, CCL2 and CXCL10, all p<0.005). In vitro assays demonstrated that imbalanced FA could underlie IFNγ production by CD4⁺ T-cells. Finally, changes on NEFA levels were associated with clinical response upon TNFα-blockade.

An altered NEFA profile can be found in RA patients associated with clinical characteristics of aggressive disease and enhanced Th1 response. These results support the relevance of lipidomic studies in RA and provide a rationale for new therapeutic targets.

• Adult
• Arthritis, Rheumatoid/immunology
• Arthritis, Rheumatoid/metabolism
• Chromatography, Liquid/methods
• Cytokines/metabolism
• Fatty Acids, Nonesterified/analysis
• Fatty Acids, Nonesterified/blood
• Female
• Humans
• Leptin/blood
• Male
• Middle Aged
• Resistin/blood
• Tandem Mass Spectrometry/methods
• Th1 Cells/immunology
• Th1 Cells/metabolism