Arachidonic Acid Content Research Articles

Effects of the rs174575 single nucleotide polymorphism in FADS2 on levels of long-chain PUFA: a meta-analysis.

The influence of the SNP rs174575 (C/G) within the fatty acid desaturase 2 gene on the levels of long-chain PUFA was determined through statistical meta-analysis. Six databases were searched to retrieve the relevant literature. Original data were analysed using Stata 17·0, encompassing summary statistics, tests for heterogeneity, assessment of publication bias, subgroup analysis and sensitivity analysis. A total of ten studies were identified and grouped into twelve trials. Our results showed that individuals who carried the minor G allele of rs174575 had significantly higher dihomo-γ-linolenic acid levels (P = 0·005) and lower arachidonic acid levels (P = 0·033) than individuals who were homozygous for the major allele. The subgroup analysis revealed that the G-allele carriers of rs174575 were significantly positively correlated with linoleic acid (P = 0·002) and dihomo-γ-linolenic acid (P < 0·001) and negatively correlated with arachidonic acid (P = 0·004) in the European populations group. This particular SNP showed a potential association with higher concentrations of dihomo-γ-linolenic acid (P = 0·050) and lower concentrations of arachidonic acid (P = 0·030) within the breast milk group. This meta-analysis has been registered in the PROSPERO database (ID: CRD42023470562).

Trans, Trans-Farnesol Enhances the Anti-Bacterial and Anti-Biofilm Effect of Arachidonic Acid on the Cariogenic Bacteria Streptococcus mutans and Streptococcus sobrinus.

Streptococcus mutans and Streptococcus sobrinus are Gram-positive bacteria involved in the development of dental caries, as they are able to form biofilms on tooth enamel, ferment sugars into acids, and survive under acidic conditions. This ultimately leads to a local lowering of the pH value on the tooth surface, which causes enamel cavities. One measure to reduce caries is to limit the growth of cariogenic bacteria by using two anti-bacterial agents with different mechanisms of action. The hypothesis of this study was that the anti-bacterial activity of ω-6 polyunsaturated arachidonic acid (AA) against S. mutans and S. sobrinus can be enhanced by the sesquiterpene alcohol trans, trans-farnesol (t,t-farnesol). The anti-bacterial activity of single and combined treatment was determined by the checkerboard assay. Bacterial viability was assessed by live/dead SYTO 9/propidium iodide (PI) staining on flow cytometry. Anti-biofilm activity was determined by MTT metabolic assay, crystal violet staining of biofilm biomass, SYTO 9/PI staining by spinning disk confocal microscopy (SDCM) and high-resolution scanning electron microscopy (HR-SEM). t,t-Farnesol lowered the minimum inhibitory concentration (MIC) and the minimum biofilm inhibitory concentration (MBIC) of AA at sub-MICs. AA reduced the metabolic activity of preformed mature biofilms, while t,t-farnesol had no significant effect. The enhanced anti-bacterial effect of the combined t,t-farnesol/AA treatment was further evidenced by increased PI uptake, indicating membrane perforation. The enhanced anti-biofilm effect was further verified by SDCM and HR-SEM. Gene expression studies showed reduced expression of some biofilm-related genes. Altogether, our study suggests a potential use of the two naturally occurring compounds arachidonic acid and t,t-farnesol for preventing biofilm formation by the cariogenic bacteria S. mutans and S. sobrinus. These findings have implications for caries prevention.

FADS1 Genetic Variant and Omega-3 Supplementation Are Associated with Changes in Fatty Acid Composition in Red Blood Cells of Subjects with Obesity.

Obesity is characterized by low-grade chronic inflammation, which can be modulated by lipid mediators derived from omega-3 (n-3) polyunsaturated fatty acids (PUFA). Obesity is a multifactorial disease, where genetic and environmental factors strongly interact to increase its development. In this context, the FADS1 gene encodes the delta-5 desaturase protein, which catalyzes the desaturation of PUFA. The rs174547 genetic variant of FADS1 has been associated with alterations in lipid metabolism, particularly with decreases in eicosapentaenoic acid (EPA) and arachidonic acid (AA) concentrations. To analyze the effect of an n-3-supplemented diet on the fatty acid profile and composition in red blood cells (RBCs) of obese subjects carrying the rs174547 variant of the FADS1 gene. Seventy-six subjects with obesity were divided into two groups: omega-3 (1.5 g of n-3/day) and placebo (1.5 g of sunflower oil/day). The dietary intervention consisted of a four-month follow-up. Anthropometric, biochemical, and dietary variables were evaluated monthly. The total fatty acid profile in RBC was determined using gas chromatography. The rs174547 variant was analyzed through allelic discrimination. The n-3 index (O3I) increased at the end of the intervention in both groups. Subjects carrying the CC genotype showed significant differences (minor increase) in n-6, n-3, total PUFA, EPA, DHA, and the O3I in RBCs compared to TT genotype carriers in the n-3 group. The diet supplemented with EPA and DHA is ideal for providing the direct products that bypass the synthesis step affected by the FADS1 rs174547 variant in subjects carrying the CC genotype. The O3I confirmed an increase in n-3 fatty acids in RBCs at the end of the intervention.

Association of plasma arachidonic acid levels with a bipolar disorder and the effects of a FADS gene variant

Recent genome-wide association studies (GWASs) have identified fatty acid desaturase (FADS) genes, which code key enzymes involved in polyunsaturated fatty acid (PUFA) desaturation as susceptibility genes for bipolar disorder (BD). Several quantitative changes in PUFAs suggest their involvement in BD pathogenesis. Therefore, this study aimed to clarify the relationship between BD and PUFAs by conducting lipidomics covariating with the FADS gene variant (rs174550), which is associated with PUFA levels and BD susceptibility. The concentrations of 23 fatty acids were measured using plasma samples from the BD group (n = 535) and the control group (n = 107). Differences in each PUFA concentration ratio were compared between the two groups. Also, differences in each PUFA concentration ratio were compared for each genotype in rs174550. Our results showed that the BD group had significantly lower concentrations of linoleic acid (LA) (β = −0.36, p = 0.023) and arachidonic acid (AA) (β = −0.18, p = 0.013) than the control group. Concerning the effect of FADS on the PUFA concentration ratio, carriers of C-allele at rs174550 had significantly decreased γ-linolenic acid and AA concentration ratios. A previous GWAS reported that the presence of a C-allele at rs174550 increased the BD risk. This direction is consistent with the lipidomic results of the present study. In conclusion, both the FADS and BD were considered to regulate the AA concentration. Thus, as the FADS gene variant is crucial for conducting lipidomics of BD we believe that the allele frequency of FADS must be analyzed.

Modeling enzyme competition in eicosanoid metabolism in macrophage cells using a cybernetic framework

Cellular metabolism is a complex process involving the consumption and production of metabolites, as well as the regulation of enzyme synthesis and activity. Modeling of metabolic processes is important to understand the underlying mechanisms, with a wide range of applications in metabolic engineering and health sciences. Cybernetic modeling is a powerful technique that accounts for unknown intricate regulatory mechanisms in complex cellular processes. It models regulation as goal-oriented, where the levels and activities of enzymes are modulated by the cybernetic control variables to achieve the cybernetic objective. This study used cybernetic model to study the enzyme competition between arachidonic acid (AA) and eicosapentaenoic acid (EPA) metabolism in murine macrophages. AA and EPA compete for the shared enzyme cyclooxygenase. Upon external stimuli, AA produces proinflammatory 2-series prostaglandins and EPA metabolizes to antiinflammatory 3-series prostaglandins, where proinflammatory and antiinflammatory responses are necessary for homeostasis. The cybernetic model adequately captured the experimental data for control and EPA-supplemented conditions. The model is validated by performing an F-test, conducting leave-one-out-metabolite cross-validation, and predicting an unseen experimental condition. The cybernetic variables provide insights into the competition between AA and EPA for the cyclooxygenase enzyme. Predictions from our model suggest that the system undergoes a switch from a predominantly proinflammatory state in the control to an antiinflammatory state with EPA-supplementation. The model can also be used to analytically determine the AA and EPA concentrations required for the switch to occur. The quantitative outcomes enhance understanding of proinflammatory and antiinflammatory metabolism in RAW 264.7 macrophages.

Oxylipin dynamics in dairy cows during clinical ketosis and after treatment with niacin and flunixin meglumine

Dairy cows with clinical ketosis (CK) exhibit metabolic changes, including intense adipose tissue (AT) lipolysis and systemic insulin resistance that increase plasma BHB and free fatty acids (FFA). Cows with CK also have systemic inflammation, predisposing them to inflammatory and infectious diseases. This inflammatory process is modulated in part by oxidized fatty acids (oxylipins) that regulate all aspects of inflammation. Oxylipin profiles have been characterized in healthy periparturient cows, but their dynamics during CK are unknown. CK is an acute metabolic disease requiring clinical therapy, commonly including propylene glycol (PG) as a gluconeogenic agent. Recently, we showed that including lipolysis inhibitors such as niacin (NIA) and flunixin meglumine (FM) improved CK recovery. These drugs may modulate oxylipin biosynthesis by regulating the release of PUFA (oxylipin substrates) and cyclooxygenase activity. However, their impact on oxylipin profiles in cows with CK is unknown. The objective of this study was to determine the dynamics of specific linoleic and arachidonic acid-derived oxylipins during CK and following therapy with PG, NIA, and FM. Multiparous Jersey cows (n = 72; 7.1 DIM) with CK from a commercial dairy were sampled. Inclusion criteria were CK symptoms (lethargy, depressed appetite, and reduced rumen fill) and blood BHB ≥ 1.2 mmol/L. CK cows (n = 24/treatment) were randomly assigned to one of the 3 treatments: 1) PG:310 g orally once daily for 5 d, 2) PG+NIA:24 g orally once daily for 3 d, 3) PG+NIA+FM:1.1 mg/kg IV once daily for 3 d. Healthy cows (HC; n = 24) matched by lactation and DIM (±2 d) were also included. Plasma oxylipins were quantified at enrollment and 7d (d7) later using HPLC-MS/MS. At enrollment, CK had higher concentrations of arachidonic acid (AA) derived 5- and 20-HETE, 8,9-, 11,12-, and 14–15-DHET, and lower concentrations of linoleic acid (LA) derived 12,13-EpOME, 13-oxoODE 9,10- and 12,13-DiHOME. Integrated analysis of biological pathways and oxylipin profiles using Ingenuity Pathway Analysis (IPA) revealed AA metabolism as the top pathway activated during CK. By d7, treatment with PGNIAFM restored plasma PUFAs and oxylipins to profiles similar to HC. IPA analysis showed that PGNIAFM activated the zinc transporter SLC30A7, associated with reduced activation of the AA pathway. Results indicate that higher FA availability during CK, driven in part by dysregulated lipolysis, increases the pool of substrates for oxylipin biosynthesis. These oxylipins may play a role in both metabolic dysregulation and restoring homeostasis during CK. Inhibiting lipolysis and cyclooxygenase activity with NIA and FM can alter AA and LA-derived oxylipins biosynthesis. These findings underscore the potential use of lipolysis inhibitors NIA and FM in CK therapeutics and highlight the importance of understanding oxylipin pathways in the pathogenesis of CK.

Canola meal extract as a low-cost substrate in Mortierella alpina culture for the production of arachidonic acid

The demand for high-quality and cost-effective raw materials is growing across various industries. Canola meal (CM), a low-cost by-product of canola processing facilities, boasts an impressive nutritional profile comprising protein, carbohydrates, vitamins, and minerals, making it a potential candidate for microbial culture media. Saskatchewan leads globally in canola production and plans to expand its canola processing facilities. Commercial valorization of CM could not only optimize the management of this by-product but also offer additional incentives and financial returns to regional canola stakeholders. Efficient utilization of canola meal extract (CME) in producing polyunsaturated fatty acids (PUFAs), such as arachidonic acid (ARA), holds promise as valuable ingredients or base chemicals for the food, feed, and nutraceutical industries. This study focused on incorporating pH 10.5 treated alkaline extract (AE) and temperature 160°C treated subcritical extract (SE) of CM into the culture medium of Mortierella alpina, an oleaginous fungus, by replacing conventional yeast extract (YE). Trials investigated the effect of aeration levels ranging from 0.5 to 2.0 vvm and revealed that increasing oxygen supply significantly boosted fungal growth rate and ARA content in biomass up to 0.39 day⁻¹ and 21.86 %, respectively. ARA production correlated positively with biomass accumulation and lipid content. Replacing YE with CME resulted in less significant differences (P < 0.05) in biomass and lipid accumulation. Additionally, AE- and SE-supplemented media exhibited higher ARA accumulation of 144.91 mg/L and 165.8 mg/L, respectively, compared to standard media (124.87 mg/L). Therefore, this study introduces canola meal extract (CME) as a novel nitrogen source in microbial media, with comparative demonstrations showing its efficiency to be similar to that of conventional extracts.

PSIII-10 Flaxseed oil-based supplement alters water consumption and plasma fatty acid profile of beef heifers

Abstract The objective of this study was to determine the effects of a flaxseed oil-based supplement (FlaxLic, New Generations, SD) on reproductive parameters, feeding behavior, and lipid profile in beef heifers. Crossbred Angus heifers [n = 60 body weight (BW) = 397kg ± 5.2 kg) were blocked by BW and antral follicle count and randomly assigned to two supplementation treatments: free-choice commercial lose mineral supplement (CON; n = 30) or free-choice flaxseed oil-based supplement (FLAX; n = 30) for 7 wk. Heifers were individually fed via the Insentec feeding system (Insentec RIC, Hokofarm, Marknesse, Netherlands), where basal diet (TMR) and supplements were provided in separate feeders to measure supplement intake and feeding behavior. Further, water intake and behavior were measured via Insentec water system. Individual intake was compiled over 24 h for each animal. Body weight, transrectal ultrasonography, and blood samples were collected weekly. On wk 5, heifers were enrolled in a fixed-time artificial insemination (FTAI) commercial protocol. Largest follicle diameter (LF) and corpus luteum (CL) presence were recorded weekly and on d of the FTAI protocol (d 0, d 7, and d 0). Pregnancy diagnosis was performed 30 d and 60 d following AI. Blood samples were analyzed for progesterone (P4) by radioimmunoassay (RIA) to determine puberty attainment before wk 5, and fatty acid profile was determined via gas chromatography-flame ionization detection. Heifers with a CL or P4 ≤ 1.0 ng/mL were considered pubertal. Data were analyzed using SAS 9.4. ADG was similar between groups (P = 0.90) but was affected by week (P &amp;lt; 0.01). TMR intake was similar in duration and quantity (P &amp;gt; 0.18) between groups. Supplement intake was greater (P &amp;lt; 0.01) for FLAX (0.73 ± 0.03 kg/d) compared with CON (0.18 ± 0.02 kg/d) and from wk 2 to wk 8 (P = 0.01). Time spent consuming the supplements was greater for FLAX compared with CON heifers (62.65 ± 2.11 vs 0.10 ± 0.11 min/d, respectively) over the entire trial (P &amp;lt; 0.01). Further, FLAX heifers consumed less water than CON heifers (32.2 ± 0.39 vs 33.93 ± 0.35 kg/d, respectively; P = 0.03) and from wk 2 to wk 7 (P = 0.03). LF was not different between groups on any of the days of the protocol (d 0, d 7, d 0; P &amp;gt; 0.20). Additionally, P4 (P ≤ 0.20), puberty attainment by wk 5 (P = 0.24), and pregnancy rates (P &amp;gt; 0.48) were similar between groups. Concentrations of arachidonic acid (3.00 ± 0.24 vs 2.32 ± 0.19 mg/mL; P = 0.04), linoleic (60.11 ± 4.34 vs 40.35 ± 4.04 mg/mL; P = 0.002), αLinolenic (16.73 ± 0.26 vs 15.86 ± 0.23 mg/mL; P = 0.02), and total polyunsaturated fatty acids (PUFA; 130.52 ± 5.97 vs 111.19 ± 5.56 mg/mL; P = 0.02) were greater on wk 8 for FLAX compared with CON heifers. Collectively, these findings did not show evidence that the flaxseed oil-based supplement affects variables that impact reproductive performance. However, it altered the plasma lipid profile, increasing omega-3, arachidonic, and linoleic fatty acids, as well as total PUFA.

Structured Triacylglycerol with Optimal Arachidonic Acid and Docosahexaenoic Acid Content for Infant Formula Development: A Bio-Accessibility Study.

Polyunsaturated fatty acids (PUFAs), especially arachidonic acid (ARA) and docosahexaenoic acid (DHA), are extremely important fatty acids for brain development in the fetus and early childhood. Premature infants face challenges obtaining these two fatty acids from their mothers. It has been reported that supplementation with triacylglycerols (TAGs) with an ARA:DHA (w/w) ratio of 2:1 may be optimal for preterm infants, as presented in commercial formulas such as Formulaid™. This study explored methods to produce TAGs with a 2:1 ratio (ARA:DHA), particularly at the more bioavailable sn-2 position of the glycerol backbone. Blending and enzymatic acidolysis of microalgae oil (rich in DHA) and ARA-rich oil yielded products with the desired ARA:DHA ratio, enhancing sn-2 composition compared to Formulaid™ (1.6 for blending and 2.3 for acidolysis versus 0.9 in Formulaid™). Optimal acidolysis conditions were 45 °C, a 1:3 substrate molar ratio, 10% Candida antarctica lipase, and 4 h. The process was reproducible, and scalable, and the lipase could be reused. In vitro digestion showed that 75.5% of the final product mixture was bio-accessible, comprising 19.1% monoacylglycerols, ~50% free fatty acids, 14.6% TAGs, and 10.1% diacylglycerols, indicating better bio-accessibility than precursor oils.

Intravenous lipid emulsions designed to meet preterm infant requirements increase plasma and tissue levels of docosahexaenoic acid and arachidonic acid in mice

Intravenous lipid emulsions used in preterm infants contain insufficient docosahexaenoic acid (DHA) and arachidonic acid (ARA) to support normal development, resulting in deficiencies that contribute to complications of prematurity and cognitive delay. We sought to investigate the effects of new intravenous lipid emulsions designed to contain sufficient DHA and ARA to meet preterm needs, while avoiding liver toxicity. Three new lipid emulsions (NLE A-C) were laboratory-generated using high pressure homogenization. First, a long-term experiment evaluated the impact on plasma, liver, and frontal cortex fatty acid composition compared to commercially available lipid emulsions. Lipid emulsions were administered via daily orogastric gavage to four-week-old C57Bl/6J mice. Next, liver toxicity was evaluated in a murine model of parenteral nutrition-induced hepatosteatosis. Mice were provided an ad lib fat-free high carbohydrate diet, with intravenous lipid emulsion administration every other day for 19 days. Administration of commercially available lipid emulsions (soybean oil, mixed oil, or fish oil) resulted in decreased plasma and tissue levels of DHA and/or ARA compared to a chow control. The new lipid emulsions demonstrated a dose-response effect in plasma and tissue concentration of DHA and ARA. NLE C (with an approximately even DHA:ARA ratio), compared to chow, maintained similar DHA (19.2±0.3 vs. 19.3±0.3%, P=1.00) and ARA (10.4±0.2 vs. 9.9±0.2% ARA, P=0.75) content in frontal cortex tissue. All three new lipid emulsions prevented biochemical liver injury and pathologist-assessed hepatosteatosis; soybean oil lipid emulsion and mixed oil lipid emulsion treatment resulted in hepatosteatosis in both experiments. Long-term treatment with the new lipid emulsions in juvenile mice resulted in increased plasma and tissue DHA and/or ARA content compared to currently available lipid emulsions. The new lipid emulsions also prevented hepatosteatosis and biochemical liver injury with enteral and parenteral administration.

Arachidonic acid regulates pluripotency by modulating cellular energetics via fatty acid synthesis and mitochondrial fission

Arachidonic acid (AA) is an important omega-6 fatty acid that can be metabolised into an impressive spectrum of biologically active mediators participating in various cellular functions. Studies have shown that fatty acid synthesis is enhanced in embryonic stem cells (ESCs), and it is crucial for the cellular reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). Fatty acid synthesis increases the cellular lipid contents and, in turn, promotes mitochondrial fission and cellular reprogramming. AA was found to induce acetyl-CoA carboxylase 1 (ACC1) expression, a major enzyme in fatty acid synthesis. In this study, we have investigated the regulation of pluripotency, fatty acid synthesis and mitochondrial activities of the human induced pluripotent stem cells (hiPSCs) and the human embryonal carcinoma (hEC) NTERA-2 cells upon treatment with varying concentrations of AA. Our results indicate that a lower concentration of AA can increase pluripotency, as evidenced by an increased expression of pluripotency markers, increased fatty acid synthesis as evidenced by lipid estimation and modulated mitochondrial fission, as evidenced by mitotracker staining for fissioned mitochondria. Moreover, higher concentrations of AA-induced the opposite effect, leading to pluripotent stem cell differentiation. Molecular docking simulations predicted the possible interactions between AA and its metabolites with fatty acid synthesis regulators ACC1 and CREB1 (Cyclic adenosine monophosphate Response Element Binding Protein 1) as a mechanism for AA regulating pluripotency.

Cannabigerol as an anti-inflammatory agent altering the level of arachidonic acid derivatives in the colon tissue of rats subjected to a high-fat high-sucrose diet

Fat and sugar overconsumption is the cause of increasing worldwide incidence of gastrointestinal tract in inflammatory conditions. The intestinal pre-inflammatory alterations are partially reversible, simultaneously inhibiting the predisposition to colitis. Searching for an effective pharmacotherapy for treating inflammatory conditions in the intestine is essential. This study aimed to investigate the effect of cannabigerol (CBG) on the inflammation state in the colon tissue of rats subjected to high-caloric diet. The experiment was conducted on male Wistar rats subjected to a standard or a high-fat high-sucrose diets for six weeks. For the last 14 days, half of rats from both groups received intragastrically cannabigerol solution (30 mg/kg of body mass). The ratio of n-6/n-3 PUFA, the activity of n-6 and n-3 PUFA, and arachidonic acid (AA) content in selected lipid fractions were determined by gas-liquid chromatography. Immunoblotting examined the expression of proteins involved in inflammation development. ELISA kits measured the content of arachidonic acid derivatives. CBG treatment reduced the n-6/n-3 PUFA ratio in TAG fraction and increased the n-3 PUFA pathway activity in almost all lipid fractions. Cannabigerol supplementation decreased AA concentration in PL and TAG. CBG also caused diminishments in the expression of cPLA2, COX-1, COX-2, and 12/15-LOX, which was indirectly correlated with a decreased LTB4 level and an increased LXA4 level. We concluded that cannabigerol has a protective influence on the development of inflammation in the colon tissue under lipid and sugar overload condition, thereby favoring cancer initiation and progression.

Genetic diversity of a Silybum marianum (L.) Gaertn. germplasm collection revealed by DNA Diversity Array Technology (DArTseq).

Silybum marianum (L.) Gaertn. is a multipurpose crop native to the Mediterranean and middle east regions and mainly known for the hepatoprotective properties of fruit-derived silymarin. Despite growing interest in milk thistle as a versatile crop with medicinal value, its potential in agroindustry is hindered by incomplete domestication and limited genomic knowledge, impeding the development of competitive breeding programs. The present study aimed to evaluate genetic diversity in a panel of S. marianum accessions (n = 31), previously characterized for morphological and phytochemical traits, using 5,178 polymorphic DArTseq SNP markers. The genetic structure investigated using both parametric and non-parametric approaches (e.g. PCA, AWclust, Admixture), revealed three distinctive groups reflecting geographical origins. Indeed, Pop1 grouped accessions from Central Europe and UK, Pop3 consisted mainly of accessions of Italian origin, and Pop2 included accessions from different geographical areas. Interestingly, Italian genotypes showed a divergent phenotypic distribution, particularly in fruit oleic and linoleic acid content, compared to the other two groups. Genetic differentiation among the three groups, investigated by computing pairwise fixation index (FST), confirmed a greater differentiation of Pop3 compared to other subpopulations, also based on other diversity indices (e.g. private alleles, heterozygosity). Finally, 22 markers were declared as putatively under natural selection, of which seven significantly affected some important phenotypic traits such as oleic, arachidonic, behenic and linoleic acid content. These findings suggest that these markers, and overall, the seven SNP markers identified within Pop3, could be exploited in specific breeding programs, potentially aimed at diversifying the use of milk thistle. Indeed, incorporating genetic material from Pop3 haplotypes carrying the selected loci into milk thistle breeding populations might be the basis for developing milk thistle lines with higher levels of oleic, arachidonic, and behenic acids, and lower levels of linoleic acid, paving new avenues for enhancing the nutritional and agronomic characteristics of milk thistle.

Association of breast milk-derived arachidonic acid-induced infant gut dysbiosis with the onset of atopic dermatitis

ObjectiveThe specific breast milk-derived metabolites that mediate host–microbiota interactions and contribute to the onset of atopic dermatitis (AD) remain unknown and require further investigation.DesignWe enrolled 250 mother–infant pairs and collected...

Serum Levels of Arachidonic Acid, Interleukin-6, and C-Reactive Protein as Potential Indicators of Pulmonary Viral Infections: Comparative Analysis of Influenza A, Respiratory Syncytial Virus Infection, and COVID-19.

Acute respiratory tract infections, including influenza A (FluA), respiratory syncytial virus (RSV) infection, and COVID-19, can aggravate to levels requiring hospitalization, increasing morbidity and mortality. Identifying biomarkers for an accurate diagnosis and prognosis of these infections is a clinical need. We performed a cross-sectional study aimed to investigate the changes in circulating levels of arachidonic acid, interleukin 6 (IL-6), and C-reactive protein (CRP) in patients with FluA, RSV, or COVID-19, and to analyze the potential of these parameters as diagnosis or prognosis biomarkers. We analyzed serum samples from 172 FluA, 80 RSV, and 217 COVID-19 patients, and 104 healthy volunteers. Individuals with lung viral diseases showed reduced arachidonic acid concentrations compared to healthy people, with these differences being most pronounced in the order COVID-19 > RSV > FluA. Conversely, IL-6 and CRP levels were elevated across diseases, with IL-6 emerging as the most promising diagnostic biomarker, with areas under the curve (AUC) of the receiver operating characteristics plot higher than 0.85 and surpassing arachidonic acid and CRP. Moreover, IL-6 displayed notable efficacy in distinguishing between FluA patients who survived and those who did not (AUC = 0.80). These findings may provide useful tools for diagnosing and monitoring the severity of acute viral respiratory tract infections, ultimately improving patient outcomes.

Dihydroartemisinin modulated arachidonic acid metabolism and mitigated liver inflammation by inhibiting the activation of 5-LOX and COX-2

BackgroundDihydroartemisinin (DHA), a derivative of Artemisia annua, has been shown to possess anti-inflammatory properties. Besides, Yes-associated protein 1 (YAP1) plays a crucial role in maintaining liver homeostasis. MethodsThis study used Yap1Flox/Flox, Albumin-Cre mice with hepatocyte-specific Yap1 knockout (referred to as Yap1LKO) and their control mice (Yap1Flox/Flox, referred to as Yap1Flox). The effect of Yap1 on lipid metabolism homeostasis was investigated through non-targeted metabolomic analysis of mouse liver. Subsequently, DHA was administered to Yap1LKO mice to assess its potential as a treatment. Liver pathology was evaluated via H&E staining, and the levels of AST, ALT, and TG were quantified using biochemical assays. The contents of arachidonic acid (AA), prostaglandin E1 (PGE1), and leukotrienes (LT) in the liver were measured using ELISA, while the protein expressions of PLIN2, 5-lipoxygenase (5-LOX), and cyclooxygenase-2 (COX-2) were analyzed through IHC staining. ResultsHepatocyte-specific Yap1 knockout activated the AA metabolic pathway, resulting in increased elevated levels of AA, PGE1, and LT levels, along with inflammatory cytokine infiltration. DHA mitigated the elevation of metabolites such as PGE1 and LT caused by the AA metabolic pathway activation by down-regulating the levels of COX-2 and 5-LOX in the liver of Yap1LKO mice. Moreover, it alleviated the accumulation of lipid vacuoles and reduced triglyceride (TG) and perilipin-2 (PLIN2) levels in the liver of Yap1LKO mice. ConclusionsExcessively low YAP1 expression induces liver inflammation and disturbances in lipid metabolism, whereas DHA modulated AA metabolism and mitigated liver inflammation by inhibiting the activation of 5-LOX and COX-2.

Cannabigerol-A useful agent restoring the muscular phospholipids milieu in obese and insulin-resistant Wistar rats?

Numerous strategies have been proposed to minimize obesity-associated health effects, among which phytocannabinoids appear to be effective and safe compounds. In particular, cannabigerol (CBG) emerges as a potent modulator of the composition of membrane phospholipids (PLs), which plays a critical role in the development of insulin resistance. Therefore, here we consider the role of CBG treatment on the composition of PLs fraction with particular emphasis on phospholipid subclasses (e.g., phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI)) in the red gastrocnemius muscle of Wistar rats fed the standard or high-fat, high-sucrose (HFHS) diet. The intramuscular PLs content was determined by gas-liquid chromatography and based on the composition of individual FAs, we assessed the stearoyl-CoA desaturase 1 (SCD1) index as well as the activity of n-3 and n-6 polyunsaturated fatty acids (PUFAs) pathways. Expression of various proteins engaged in the inflammatory pathway, FAs elongation, and desaturation processes was measured using Western blotting. Our research has demonstrated the important association of obesity with alterations in the composition of muscular PLs, which was significantly improved by CBG supplementation, enriching the lipid pools in n-3 PUFAs and decreasing the content of arachidonic acid (AA), which in turn influenced the activity of PUFAs pathways in various PLs subclasses. CBG also inhibited the local inflammation development and profoundly reduced the SCD1 activity. Collectively, restoring the PLs homeostasis of the myocyte membrane by CBG indicates its new potential medical application in the treatment of obesity-related metabolic disorders.

Rosehip tea as a possible cause of acute interstitial nephritis

BackgroundAcute interstitial nephritis (AIN) is characterized by an inflammatory infiltrate in the renal interstitium. The etiology of AIN is broad with the most common cause being medications. Treatment includes removal of the offending agent, glucocorticoid therapy, and immunosuppression. Rosehips are a fruit produced from wild roses that are often used in teas and herbal supplements. They are reported to have anti-inflammatory effects and sought after for this purported benefit.Case presentationWe present a case of a 67-year-old woman who presented with acute kidney injury after two months of excessive rosehip tea consumption. She was dialyzed for 1 month and treated with oral steroids. Her initial renal biopsy revealed AIN, a thin glomerular basement membrane, and five nodular sclerosed glomeruli. Her work-up was negative for known causes of AIN and the etiology was determined to be rosehip tea. Two months after initial presentation she continued to have clinical and pathologic signs of AIN. She was started on mycophenolate mofetil (MMF) with clinical improvement.ConclusionRosehip tea is known to have diuretic properties and, when consumed, may lead to a self-perpetuating cycle of intake. Excessive consumption may lead to increased concentrations of arachidonic acid and its metabolites. These metabolites have been shown to perpetuate an inflammatory response capable of causing AIN. Providers should be aware when counseling patients that excessive intake of rosehip tea may lead to AIN.

Fatty Acid Profile of Erythrocyte Membranes in Patients with Psoriasis.

Psoriasis is a chronic systemic disease with a multifaceted pathomechanism and immunological basis, with the presence of inflammatory skin lesions and joint ailments. Diseases accompanying psoriasis include metabolic and cardiovascular disorders. It has been suggested that inflammation is involved in the development of each of these conditions. The main objective of this study was to analyse the fatty acid profile, including polyunsaturated fatty acids, in the erythrocyte membranes of patients suffering from psoriasis. A total of 58 adult patients of the Department of Skin and Venereal Diseases of the Pomeranian Medical University in Szczecin, suffering from psoriasis, were qualified for this study. The patients had undergone an interview and physical examination, during which the severity of psoriasis was assessed. All patients had their weight and height measured to assess their body mass index (BMI). After 3 months of treatment, biochemical parameters (ALT, AST, total cholesterol) and inflammatory markers (CRP) in the blood were assessed. In addition, the isolation of fatty acids (PUFAs, SFAs, MUFAs) from erythrocyte membranes and the qualitative and quantitative analysis of their profile using a gas chromatograph were carried out. In patients with severe psoriasis requiring systemic treatment, an altered profile of fatty acids in erythrocyte membranes was found, including a significantly lower concentration of polyunsaturated fatty acids (omega-3), which have an anti-inflammatory effect; a significantly higher concentration of saturated fatty acids; and a decreased concentration of oleic acid (omega-9), compared to the results obtained in patients with less severe psoriasis receiving topical treatment. In patients with psoriasis and BMI ≥ 25, significantly higher concentrations of AST and ALT in the blood and significantly higher concentrations of pro-inflammatory arachidonic acid in erythrocyte membranes were found. Elevated concentrations of saturated (R = 0.31) and monounsaturated fatty acids (R = 0.29) may correlate with a greater severity of psoriasis.

The Impact of Lactobacillus delbrueckii Hepatic Metabolism in Post-Weaning Piglets

Lactobacillus delbrueckii garners interest for its contributions to gut microecological balance, diarrheal prevention and treatment, immune modulation, growth promotion, and meat quality enhancement in livestock. However, its impact on the gut microbiota and liver metabolism in weaned piglets is less documented. This study involved 80 Duroc-Landrace-Yorkshire weaned piglets aged 28 days, randomized into two groups with four replicates each and ten piglets per replicate. Over a 28-day period, the piglets were fed either a basal diet (control group) or the same diet supplemented with 0.1% Lactobacillus delbrueckii microcapsules (≥1.0 × 1010 CFU/g) (Lactobacillus delbrueckii group). The principal findings are as follows: During the initial phase of the experiment, supplementation with Lactobacillus delbrueckii increased the levels of L-phenylalanine and L-lysine in the liver while reducing the L-alanine levels, thereby enhancing the aminoacyl–tRNA synthesis pathway in weaned piglets. In the later phase, Lactobacillus delbrueckii supplementation boosted the liver arachidonic acid content, strengthening the arachidonic acid metabolic pathway in the piglets. The gut microbiota and their metabolites likely play a role in regulating these processes. These results indicate that, compared to the control group, Lactobacillus delbrueckii reduced weaning stress-induced liver damage and metabolic disorders, increased liver glycogen content, and enhanced liver antioxidant function by improving the metabolism of lipids and carbohydrates. Consequently, the liver functioned more healthily.