Evaluation of synergistic/antagonistic antibacterial activities of fatty oils from apricot, date, grape, and black seeds.

The increasing antimicrobial resistance requires continuous investigation of new antimicrobial agents preferably derived from natural sources. New powerful antibacterial agents can be produced by simply combining oils that are known for their antibacterial activities. In this study, apricot seed oil (ASO), date seed oil (DSO), grape seed oil (GSO), and black seed oil (BSO) alone and in binary mixtures were assessed. Fatty acid profiles of individual oils and oil mixtures showed linoleic acid, oleic acid, palmitic acid, stearic acid, and linolenic acid contents. Linoleic acid was the most abundant fatty acid in all samples except for ASO, where oleic acid was the dominant one. GSO showed the highest total phenolic content while ASO showed the lowest one. Antibacterial screening was performed against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Staphylococcus aureus. Results showed antibacterial activity in all oils against tested strains except for ASO against S. aureus. Highest antibacterial activity recorded was for ASO against P. mirabilis. ASO-GSO mixture (AG) was the best mixture where it showed synergistic interactions against all strains except P. aeruginosa. In conclusion, seed oil mixtures are likely to show promising antibacterial activities against specific strains.

Dietary Resveratrol Ameliorates Hepatic Fatty Acid Metabolism and Jejunal Barrier in Offspring Induced by Maternal Oxidized Soybean Oil Challenge.

Increasing evidence indicates that maternal exposure to oxidized soybean oil (OSO) causes damage to the mother and offspring. The antioxidant resveratrol (Res) has a variety of health benefits. However, the protective effect of Res on mitigating offspring damage after maternal exposure to OSO and its mechanism remains unclear. Therefore, this study aimed to investigate the effect of Res on hepatic fatty acid metabolism and the jejunal barrier in suckling piglets after maternal OSO exposure. A total of 18 sows in late gestation were randomly assigned to three treatments. The sows were fed with a fresh soybean oil (FSO) diet, an OSO diet, or the OSO diet supplemented with 300 mg/kg Res (OSO + Res), respectively. The results showed that maternal supplementation of Res restored the mRNA levels of genes related to fatty acid metabolism and increased the activities of catalase (CAT) and total superoxide dismutase (T-SOD) in suckling piglets' livers under the OSO challenge. Moreover, the OSO + Res group restored the mRNA levels of occludin and claudin 4 in suckling piglet jejunum compared with the results of the OSO challenges. In summary, supplementation with Res improves hepatic fatty acid metabolism and intestinal barrier function of suckling piglets after maternal OSO challenge during late gestation and lactation.

Fatty acid/monoglyceride type and amount modulate fat-soluble vitamin absorption from mixed assemblies in mice.

We investigated the effects of fatty acid/ monoglyceride type and amount on the absorption of fat-soluble vitamins. Micelles or vesicles made with either caprylic acid (CA) + monocaprylin (MC) or oleic acid (OA) + monoolein (MO) at low or high concentrations were infused in bile duct-ligated mice. Retinol + retinyl ester and γ-tocopherol intestinal mucosa contents were higher in mice infused with CA + MC than with OA + MO (up to + 350 % for vitamin A and up to + 62 %, for vitamin E; p < 0.05). Cholecalciferol intestinal mucosa content was the highest in mice infused with micelles with CA + MC at 5 mg/mL (up to + 105 %, p < 0.05). Retinyl ester plasma response was higher with mixed assemblies formed at low concentration of FA + MG compared to high concentration (up to + 1212 %, p < 0.05), while no difference in cholecalciferol and γ-tocopherol plasma responses were measured. No correlation between size or zeta potential and vitamin absorption was found. The impact of FA and MG on fat-soluble vitamin absorption thus differs from one vitamin to another and should be considered to formulate adequate vitamin oral or enteral supplements.

Exploring the in vitro potential of royal jelly against glioblastoma and neuroblastoma: impact on cell proliferation, apoptosis, cell cycle, and the biomolecular content.

Neuroblastoma and glioblastoma are the most commonly seen nervous system tumors, and their treatment is challenging. Relatively safe and easy acquisition of nutraceutical natural products make them suitable candidates for anticancer research. Royal jelly (RJ), a superfood, has many biological and pharmacological activities. This study was conducted to, for the first time, elucidate its anticancer efficiency, even in high doses, on neuroblastoma and glioblastoma cell lines through cell viability, apoptosis, cell cycle and biomolecular content evaluation. We performed experiments with RJ concentrations in the range of 1.25-10 mg mL-1 for 48 h. Cell viability assays revealed a notable cytotoxic effect of RJ in a concentration-dependent manner. Treatment with a high dose of RJ significantly increased the apoptotic cell population of both cell lines. Furthermore, we observed G0-G1 phase arrest in neuroblastoma cells but G2-M arrest in glioblastoma cells. All these cellular changes are closely associated with the alterations of the macromolecular makeup of the cells, such as decreased saturated lipid, protein, DNA and RNA amounts, protein conformational changes, decreased protein phosphorylation and increased protein carbonylation. These cellular changes are associated with RJ triggered-ROS formation. The clear segregation between the control and the RJ-treated groups proved these changes, obtained from the unsupervised and supervised chemometric analysis. RJ has good anticancer activity against nervous system cancers and could be safely used with current treatment strategies.

Camellia oil with its rich in fatty acids enhances post-thawed boar sperm quality.

BACKGROUND: Boar sperm are highly susceptible to specific conditions during cryopreservation, leading to a significant decrease in their fertilizing potential due to damage to their membranes. Camellia oil, known for its fatty acids with antioxidant and biological properties, has not been previously explored for the cryopreservation of boar semen. This study aimed to examine the effects of camellia oil on post-thawed boar sperm quality. Boar semen ejaculates (n = 9) were collected and divided into six equal aliquots based on camellia oil concentrations (0, 0.5, 1, 1.5, 2 and 2.5% v/v) in the freezing extender. Semen samples were processed and cryopreserved using the liquid nitrogen vapor method. Thereafter, frozen semen samples were thawed at 50 °C for 12 s and evaluated for sperm morphology by scanning electron microscope, sperm motility using a computer-assisted sperm analyzer, sperm viability, acrosome integrity, mitochondrial function, MDA level and total antioxidant capacity. RESULTS: The results demonstrated that the supplementation of 1.5% (v/v) camellia oil showed superior post-thaw sperm qualities such as improved sperm morphology, motility, acrosome integrity and mitochondrial function by 14.3%, 14.3% and 11.7%, respectively, when compared to the control group. Camellia oil at a concentration of 1.5% (v/v) showed the lowest level of MDA (18.3 ± 2.1 µmol/L) compared to the other groups. CONCLUSIONS: In conclusion, adding 1.5% (v/v) camellia oil in the freezing extender reduced the oxidative damage associated with cryopreservation and resulted in a higher post-thawed sperm quality.

Dietary Chinese herbal formula supplementation improves yolk fatty acid profile in aged laying hens.

Chinese herbal formula (CHF) has the potential to improve the performance of aged laying hens through integrated regulation of various physiological functions. The present study aimed to investigate the effects of dietary CHF supplementation on the yolk fatty acid profile in aged laying hens. A total of 144 healthy 307-day-old Xinyang black-feather laying hens were randomly allocated into two groups: a control group (CON, fed a basal diet) and a CHF group (fed a basal diet supplemented with 1% CHF; contained 0.30% Leonurus japonicus Houtt., 0.20% Salvia miltiorrhiza Bge., 0.25% Ligustrum lucidum Ait., and 0.25% Taraxacum mongolicum Hand.-Mazz. for 120 days). The fatty acid concentrations in egg yolks were analyzed using a targeted metabolomics technology at days 60 and 120 of the trial. The results showed that dietary CHF supplementation increased (p < .05) the concentrations of several saturated fatty acids (SFA, including myristic acid and stearic acid), monounsaturated fatty acids (MUFA, including petroselinic acid, elaidic acid, trans-11-eicosenoic acid, and cis-11-eicosenoic acid), polyunsaturated fatty acids (PUFA, including linolelaidic acid, linoleic acid, γ-linolenic acid, α-linolenic acid, 11c,14c-eicosadienoic acid, eicosatrienoic acid, homo-γ-linolenic acid, arachidonic acid, and docosapentaenoic acid), and fatty acid indexes (total MUFA, n-3 and n-6 PUFA, PUFA/SFA, hypocholesterolemic/hypercholesterolaemic ratio, health promotion index, and desirable fatty acids) in egg yolks. Collectively, these findings suggest that dietary CHF supplementation could improve the nutritional value of fatty acids in egg yolks of aged laying hens, which would be beneficial for the production of healthier eggs to meet consumer demands.

Metabolomics responses and tolerance of Pseudomonas aeruginosa under acoustic vibration stress.

Sound has been shown to impact microbial behaviors. However, our understanding of the chemical and molecular mechanisms underlying these microbial responses to acoustic vibration is limited. In this study, we used untargeted metabolomics analysis to investigate the effects of 100-Hz acoustic vibration on the intra- and extracellular hydrophobic metabolites of P. aeruginosa PAO1. Our findings revealed increased levels of fatty acids and their derivatives, quinolones, and N-acylethanolamines upon sound exposure, while rhamnolipids (RLs) showed decreased levels. Further quantitative real-time polymerase chain reaction experiments showed slight downregulation of the rhlA gene (1.3-fold) and upregulation of fabY (1.5-fold), fadE (1.7-fold), and pqsA (1.4-fold) genes, which are associated with RL, fatty acid, and quinolone biosynthesis. However, no alterations in the genes related to the rpoS regulators or quorum-sensing networks were observed. Supplementing sodium oleate to P. aeruginosa cultures to simulate the effects of sound resulted in increased tolerance of P. aeruginosa in the presence of sound at 48 h, suggesting a potential novel response-tolerance correlation. In contrast, adding RL, which went against the response direction, did not affect its growth. Overall, these findings provide potential implications for the control and manipulation of virulence and bacterial characteristics for medical and industrial applications.

Gypenoside XIII regulates lipid metabolism in HepG2 hepatocytes and ameliorates nonalcoholic steatohepatitis in mice.

Gypenoside XIII is isolated from Gynostemma pentaphyllum (Thunb.) Makino. In mice, G. pentaphyllum extract and gypenoside LXXV have been shown to improve non-alcoholic steatohepatitis (NASH). This study investigated whether gypenoside XIII can regulate lipid accumulation in fatty liver cells or attenuate NASH in mice. We used HepG2 hepatocytes to establish a fatty liver cell model using 0.5 mM oleic acid. Fatty liver cells were treated with different concentrations of gypenoside XIII to evaluate the molecular mechanisms of lipid metabolism. In addition, a methionine/choline-deficient diet induced NASH in C57BL/6 mice, which were given 10 mg/kg gypenoside XIII by intraperitoneal injection. In fatty liver cells, gypenoside XIII effectively suppressed lipid accumulation and lipid peroxidation. Furthermore, gypenoside XIII significantly increased SIRT1 and AMPK phosphorylation to decrease acetyl-CoA carboxylase phosphorylation, reducing fatty acid synthesis activity. Gypenoside XIII also decreased lipogenesis by suppressing sterol regulatory element-binding protein 1c and fatty acid synthase production. Gypenoside XIII also increased lipolysis and fatty acid ß-oxidation by promoting adipose triglyceride lipase and carnitine palmitoyltransferase 1, respectively. In an animal model of NASH, gypenoside XIII effectively decreased the lipid vacuole size and number and reduced liver fibrosis and inflammation. These findings suggest that gypenoside XIII can regulate lipid metabolism in fatty liver cells and improve liver fibrosis in NASH mice. Therefore, gypenoside XIII has potential as a novel agent for the treatment of NASH.

Impact of dairy fat manipulation on endothelial function and lipid regulation in human aortic endothelial cells exposed to human plasma samples: an in vitro investigation from the RESET study.

PURPOSE: Longer-term intake of fatty acid (FA)-modified dairy products (SFA-reduced, MUFA-enriched) was reported to attenuate postprandial endothelial function in humans, relative to conventional (control) dairy. Thus, we performed an in vitro study in human aortic endothelial cells (HAEC) to investigate mechanisms underlying the effects observed in vivo. METHODS: This sub-study was conducted within the framework of the RESET study, a 12-week randomised controlled crossover trial with FA-modified and control dairy diets. HAEC were incubated for 24 h with post-intervention plasma samples from eleven adults (age: 57.5 ± 6.0 years; BMI: 25.7 ± 2.7 kg/m2) at moderate cardiovascular disease risk following representative sequential mixed meals. Markers of endothelial function and lipid regulation were assessed. RESULTS: Relative to control, HAEC incubation with plasma following the FA-modified treatment increased postprandial NOx production (P-interaction = 0.019), yet up-regulated relative E-selectin mRNA gene expression (P-interaction = 0.011). There was no impact on other genes measured. CONCLUSION: Incubation of HAEC with human plasma collected after longer-term dairy fat manipulation had a beneficial impact on postprandial NOx production. Further ex vivo research is needed to understand the impact of partial replacement of SFA with unsaturated fatty acids in dairy foods on pathways involved in endothelial function.

Icariside II prevents kidney fibrosis development in chronic kidney disease by promoting fatty acid oxidation.

Renal interstitial fibrosis (RIF) is the main pathological basis for the progression of chronic kidney disease (CKD), however, effective interventions are limited. Here, we investigated the effect of Icariside II (ICA-II) on RIF and explored the underlying mechanisms. Rats receiving 5/6 ablation and infarction (A/I) surgery were gavaged with ICA-II (5 or 10 mg/kg) for 8 weeks. In vitro, TGF-ß1-stimulated NRK-52E cells were treated with ICA-II and (or) oleic acid, etomoxir, ranolazine, fenofibrate, and GW6471. The effects of ICA-II on RIF, fatty acid oxidation, lipid deposition, and mitochondrial function were determined by immunoblotting, Oil red O staining, colorimetric, and fluorometric assays. Using adeno-associated virus injection and co-culture methods, we further determined mechanisms of ICA-II anti-RIF. ICA-II ameliorated the fibrotic responses in vivo and in vitro. RNA-seq analysis indicated that ICA-II regulated fatty acid degradation and PPAR pathway in 5/6 (A/I) kidneys. ICA-II attenuated lipid accumulation and up-regulated expression of PPARα, CPT-1α, Acaa2, and Acadsb proteins in vivo and in vitro. Compared to ICA-II treatment, ICA-II combined with Etomoxir exacerbated mitochondrial dysfunction and fibrotic responses in TGF-ß-treated NRK-52E cells. Importantly, we determined that ICA-II improved lipid metabolism, fatty acid oxidation, mitochondrial function, and RIF by restoring PPARα. Co-culture revealed that ICA-II decreased the expression of Fibronectin, Collagen-I, α-SMA, and PCNA proteins in NRK-49F cells by restoring PPARα of renal tubular cells. ICA-II may serve as a promising therapeutic agent for RIF in 5/6 (A/I) rats, which may be important for the prevention and treatment of CKD.

Evaluation of Fatty Acid Contents and Biological Activities of Jurinea turcica.

The fatty acid profile, antioxidant/antibacterial, and cytotoxic effects of the extracts obtained from Jurinea turcica B.Dogan& A.Duran have been evaluated for the first time in the current study. The fatty acid profile of ethanolic extracts was determined using the Soxhlet extractor by a gas chromatography-mass spectrometer. The antioxidant and antibacterial activities were measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferrous reduction tests and the disc diffusion technique. Additionally, the cytotoxicity and wound healing assays were performed on A549 cells. The highest amount of component in the leaf extract was docosanoic acid methyl ester, whereas abundant arachidonic acid methyl ester was mainly found in the flower extract. The IC50 values, the 50 % scavenging value for the DPPH radical, were 179.13 and 124.67 µg/mL for the leaf and flower extracts, respectively. IC50 values (the half-maximal inhibitory concentration) were 10.4 and 24.7 µg/mL for the flower and leaf extracts, respectively. The leaf extract showed more potent antibacterial activity on Enterococcus faecalis (17 mm) and Staphylococcus aureus (16 mm) bacteria than the flower extract. In conclusion, the extracts of J. turcica have anti-cancerogenic and antibacterial effects. Leaf extracts have antibacterial and anti-metastatic effects, while flower extracts show antioxidant, cytotoxic, and apoptotic properties in A549 cells.

Impact of Cholesterol Metabolism on H2O2-Induced Oxidative Stress Injury in HepG2 Cells Treated with Fatty Acids.

Objective: This study aimed to evaluate the expression of genes involved in cholesterol metabolism and establish their association with oxidative stress (OS). Methods: We employed an in vitro experimental design and cells were divided into six groups: C (control), CH (HepG2 + H2O2), CHN (HepG2 + H2O2 + NAC), F (FFA-treated HepG2), FH (FFA-treated HepG2 + H2O2), and FHN (FFA-treated HepG2 + H2O2 + NAC). Cell viability was assessed using the MTT assay, while successful FFA model establishment was confirmed via Oil Red staining and absorbance. Oxidative stress injury was gauged by measuring ROS, SOD activity, and MDA content. RNA transcription and protein expression of cholesterol-related (DHCR24, DHCR7) and oxidative stress-related (NFE2L2, HMOX1) genes were also examined via RT-qPCR and WB. Results: The impact of H2O2 on cell viability exhibited a time-dose-dependent pattern, paralleling the changes in reactive oxygen species (ROS) levels. Compared to the C group, FFA treatment led to an increase in Oil Red absorption and MDA content and decreased SOD activity. However, it did not result in a significant reduction in cell viability. The FH group exhibited reduced cell viability and SOD activity, along with a further elevation in MDA content compared to the F group. Furthermore, the increased SOD activity and decreased MDA content observed in the CH group were effectively reversed following NAC treatment. Such a reversal was not evident between the FHN and FH groups. Compared to the control group, genes associated with cholesterol metabolism and oxidative stress (OS) displayed heightened expression levels in the other treatment groups, with the FHN group showing lower expression levels than the FH group. Notably, changes in the protein expressions of DHCR24, DHCR7, NFE2L2, and HMOX1 were consistent and exhibited correlations. Conclusions: Cholesterol metabolism emerges as a potential mechanism underlying H2O2-induced oxidative stress injury in HepG2 cells treated with FFA.

Effects of fat source in calf starter on growth performance, blood fatty acid profiles, and inflammatory markers during cold season.

This study was conducted to investigate the effects of supplementation of different fat sources in calf starters on growth performance, health, blood fatty acid profiles, and inflammatory markers during the cold season in dairy calves. A total of 48 Holstein calves (24 males and 24 females) were randomly assigned to 1 of 4 starter diets throughout the experiment (d 3 to 65): (1) no supplemented fat (CON), (2) 3% calcium-salts of soybean oil (Ca-SBO), (3) 3% calcium-salts of fish oil (Ca-FO), and (4) 3% mixture of Ca-SBO and Ca-FO (1.5% each, DM basis; MIX). Calves were given free access to starter feed and water and were raised individually in pens from 3 to 65 d of age. Calves fed Ca-SBO consumed a greater proportion of n-6 FA, while calves fed Ca-FO consumed a greater level of n-3 FA compared to the other dietary treatments. Fat supplementation increased the intake of linoleic acid, the major n-6 FA, with the greater intake observed in the Ca-SBO group compared to the other dietary treatments. Calves fed the Ca-FO and MIX diets consumed more long-chain n-3 FA than the other diets. In addition, calves fed Ca-SBO and Ca-FO diets consumed more starter feed and total dry matter than calves fed MIX and CON throughout the experiment (d 3 to 65). Calves fed Ca-FO had higher average daily gain throughout the trial (d 3 to 65) than the other treatment groups. Of all treatment groups, calves fed Ca-FO achieved the highest final body weight and showed the greatest feed efficiency. Random forest analysis revealed that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid were the serum levels of FA most affected by the diets. The principal component analysis of blood FA profile, blood parameters, and inflammatory markers showed distinct differences between dietary treatments. Calves fed Ca-SBO had higher plasma concentrations of linoleic acid, while calves fed Ca-FO had higher plasma concentrations of long-chain n-3 polyunsaturated fatty acids (PUFA), such as EPA, docosapentaenoic acid (DPA), and DHA than the other treatment groups. Plasma inflammatory markers were lower in calves fed Ca-FO and higher in calves fed CON than in the other treatment groups. The Ca-FO group had lower levels of inflammatory markers, including serum amyloid A, tumor necrosis factor-alpha, Interferon-γ, haptoglobin, and interleukin-6 compared to the other experimental treatments. Also, the blood malondialdehyde levels, an indicator of oxidative stress, were lower in calves fed Ca-FO compared with calves fed the other treatment diets. In conclusion, the performance of preweaned dairy calves can be improved by adding fat to their starter feed under cold conditions. Overall, the type of fat in milk may affect growth and inflammation of dairy calves before weaning under cold conditions, with n-3 FA (Ca-FO) promoting growth and reducing inflammation more effectively than n-6 FA (Ca-SBO).

Date (Phoenix dactylifera L.) seed oil is an agro-industrial waste with biopreservative effects and antimicrobial activity.

Antimicrobial resistant (AMR) infections are a leading health threat globally. Previous literature has underscored the farm-to-fork continuum as a potential focal point for the emergence and spread of AMR. In the present study, date (Phoenix dactylifera L.) seed oil was investigated for its chemical composition and antimicrobial activity against common foodborne pathogens including Escherichia coli O157:H7, Salmonella enteritidis, Salmonella typhimurium, Listeria monocytogenes, and Staphylococcus aureus in vitro, and in ultra-high-temperature (UHT) milk as a food model at storage temperatures of 37 °C (24 h) and 10 °C (7 days). GC-MS analysis of the seed oil revealed 20 compounds, with octadecane (52.2-55.4%) as the major constituent, and the fatty acid analysis revealed 17 fatty acids, with oleic acid (42.3-43.1%) as the main constituent, followed by lauric acid (19.8-20.3%). The antimicrobial activity of date seed oil was determined using the microdilution method. A significant inhibition against gram-negative bacteria was noted in microbiological media and UHT milk, with a log reduction ranging from 4.3 to 6.7 (at 37 °C/24 h) and 5.7 to 7.2 (at 10 °C/7 days), respectively, at oil concentrations ranging between 10 and 15 µl/ml. The oil showed a similar significant inhibitory effect against St. aureus in the microbiological media (2.0-6.0 log reduction), whereas the inhibitory effect against L. monocytogenes was not statistically significant, with a maximum log reduction of 0.64 achieved at a concentration of 10 µl/ml. AFM imaging of the bacteria showed that oil treatment led to morphological changes in the bacteria including the formation of distorted shapes, surface blebs, indentations, stiffness, and swelling. Present findings suggest that date seed oil can be a promising by-product with potential antimicrobial activity and a food preservative.

Annona cherimola Seed Extracts Trigger an Early Apoptosis Response and Selective Anticlonogenic Activity against the Human Gastric Carcinoma Cell Line SNU-1.

The aim of this study was to evaluate, for the first time, the antiproliferative, apoptotic and diminishing effects of the anchored growth-independent capacity of an ethanol macerate extract from the Annona cherimola seed (EMCHS) in the human gastric cancer cell line SNU-1. The cells treated with EMCHS (20 µg/mL) significantly reduced the capacity to form clones of the tumor cell. Moreover, 50 µg/mL of EMCHS extract induced apoptosis, as was shown by the Annexin-V assay. UHPLC-MS/MS analysis detected two acetogenins (Annonacinone and Annonacin) in the EMCHS, which could be largely responsible for its selective antiproliferative effect. The identification of fatty acids by GC-FID showed the presence of eight fatty acids, among which was, oleic acid, which has recognized activity as an adjuvant in antitumor treatments. Taken together, our results indicate that the EMCHS seems promising for use as a natural therapy against gastric cancer disease.

The effect of oral treatment of royal jelly on the expression of the PDGF-ß gene in the skin wound of male mice.

AIMS OF THE STUDY: Royal jelly (RJ) is one of the most widely used drugs in traditional medicine. One of its important applications is the repair of skin damage, although the path of its mechanism is still unknown. Platelet-derived growth factor-beta (PDGF-beta) is one of the important factors in wound healing and it has been observed that PDGF-ß expression decreases with increasing age. In this study, for the first time, the effect of RJ on skin wounds has been investigated through the expression of PDGF-ß and tissue studies. MATERIALS AND METHODS: 25 small laboratory male BALB/c mice were selected randomly and after creating a 5 mm wound on the back of their neck, they were treated with doses of 2.5, 10, and 40 mg/kg body weight, After sampling from the healed wound in 9th day, histopathological studies and the expression of PDGF-ß gene were performed by Real-time PCR method. RESULTS: The findings of the present study showed that royal jelly caused a significant increase in PDGF-ß (10.99 times) compared to the healthy group. Also, royal jelly increased the formation of covering tissue or epithelium, the synthesis of collagen, the presence of inflammatory cells, and the formation of new blood vessels. CONCLUSION: The oral treatment of royal jelly is probably effective in skin wound healing by changing the expression of PDGF-ß.

Effects of polyunsaturated fatty acid supplementation on plasma and follicular fluid resolvin D1 concentration and mRNA abundance in granulosa cells in ewes.

The aim of this experiment was to evaluate the effect of increasing dietary omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation on plasma and follicular fluid resolvin D1 (RvD1) concentration and the mRNA expression of genes related to RvD1 production, inflammatory response, oxidative stress, hormone receptors and production, and free fatty acid receptors in the granulosa cells of ewes. Dorset × Hampshire ewes (n = 24) aged 2 to 4 yr and with an initial body weight (BW) of 84.08 ±â€…13.18 kg were blocked by body condition score (BCS) and BW, and randomly assigned to 12 pens. Each pen within each block was randomly assigned to one of three treatments: 1) diet without fatty acid supplementation (control), 2) diet with 0.5% n-3 PUFA supplementation (PUFA0.5), and 3) diet with 1% n-3 PUFA supplementation (PUFA1). BW, BCS, and blood samples were obtained on day 1 and every 21 d for 3 mo. Ewes were then synchronized, superstimulated, and ovariectomized. Antral follicles were aspirated to evaluate RvD1 concentration in follicular fluid, and granulosa cells were used to determine mRNA abundance. Data were analyzed as a randomized complete block design using a mixed model (MIXED or GLIMMIX with log as a link function when data presented a nonnormal distribution). A polynomial effect of treatments was used to analyze RvD1 concentration and mRNA expression when there was no interaction. In addition, the correlation between plasma and follicular fluid RvD1 concentration was evaluated. We found no differences in BW (P = 0.28) and BCS (P = 0.29) between treatments. The concentration of RvD1 in plasma and follicular fluid linearly increased (P = 0.03) and tended to increase (P = 0.06) concomitantly to increasing PUFA supplementation. Plasma and follicular fluid RvD1 concentrations were positively correlated (r = 0.61; P < 0.01). The abundance of GPX1 and GPR32 mRNA tended to increase linearly with increasing PUFA supplementation (P = 0.06). In addition, PUFA supplementation linearly decreased and tended to decrease IL-1ß and COX-2 mRNA abundance (P = 0.01 and P = 0.06, respectively). In conclusion, the correlation between plasma and follicular fluid RvD1 concentration indicates a relationship between both compartments. Also, the decrease of IL-1ß and the increase of GPX1 mRNA abundance after PUFA supplementation could have beneficial effects on follicle development.

The aim of this experiment was to evaluate the effects of increasing dietary omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation on plasma and follicular fluid resolvin D1 (RvD1) concentration, and the mRNA expression of genes related to RvD1 synthesis, inflammatory response, oxidative stress, reproductive hormone receptors and production, and free fatty acid receptors in ewes. Twenty-four ewes aged 2 to 4 yr were assigned to 12 pens and randomly allocated to one of three treatments: 1) diet without fatty acid supplementation (control), 2) diet with 0.5% n-3 PUFA (PUFA0.5), and 3) diet with 1% n-3 PUFA (PUFA1). Body weight (BW), body condition score (BCS), and blood samples were obtained on day 1 and every 21 d for 3 mo. Ewes were then synchronized, superstimulated, and ovariectomized. Antral follicles were aspirated to evaluate follicular fluid RvD1 concentration, and granulosa cells were used to analyze mRNA concentration. We found no differences in BW and BCS between treatments. Plasma and follicular fluid RvD1 concentration increased concomitantly to increasing dietary PUFA supplementation. There was a positive correlation between plasma and follicular fluid RvD1 concentrations. Omega-3 PUFA increased the mRNA abundance of genes associated with RvD1 synthesis and oxidative damage response. In addition, PUFA supplementation linearly decreased the mRNA abundance of genes associated with inflammatory response. In conclusion, the positive correlation between plasma and follicular fluid RvD1 concentrations demonstrates a relationship between both compartments. Also, changes in gene expression after PUFA supplementation may have a beneficial effect on the follicle and, in turn, on reproduction.

Impact of saturated compared with unsaturated dietary fat on insulin sensitivity, pancreatic ß-cell function and glucose tolerance: a systematic review and meta-analysis of randomized, controlled trials.

BACKGROUND: The impact of the dietary fat type on type 2 diabetes (T2D) remains unclear. OBJECTIVES: We aimed to evaluate the effects of replacing dietary saturated fatty acids (SFA) with mono- or poly-unsaturated fatty acids (MUFA and PUFA, respectively) on insulin sensitivity, pancreatic ß-cell function, and glucose tolerance, as surrogate endpoints for T2D. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials that replaced ≥5% of total energy intake provided by SFA with MUFA or PUFA and reported indexes of insulin sensitivity, ß-cell function, and/or glucose tolerance. We searched MEDLINE, Scopus, and the Cochrane Library (CENTRAL) up to 9 January, 2023. Eligible interventions had to be isocaloric, with no significant difference in other macronutrients. Data were synthesized using random-effects model meta-analysis. RESULTS: Of 6355 records identified, 10 parallel and 20 crossover trials with 1586 participants were included. The mean age of the participants was 42 years, 47% were male, mean body mass index (BMI; in kg/m2) was 26.8, median baseline fasting glucose was 5.13 mmol/L, and the median duration of interventions was 5 weeks. Replacing SFA with MUFA or PUFA had no significant effects on insulin sensitivity [standardized mean difference (SMD) SFA compared with MUFA: 0.01, 95% confidence interval (CI): -0.06 to 0.09, I2 = 0% and SMD SFA compared with PUFA: 0, 95% CI: -0.15 to 0.14, I2 = 0%]. Replacing SFA with MUFA did not significantly impact the ß-cell function, evaluated by the disposition index (mean difference: -12, 95% CI: -158 to 133, I2=0%). Evidence on glucose tolerance (SFA compared with MUFA or PUFA) and on ß-cell function when SFA were replaced with PUFA was scant. CONCLUSIONS: Short-term substitution of saturated with unsaturated fat does not significantly affect insulin sensitivity nor ß-cell function (the latter in the SFA compared with MUFA comparison). Future studies are needed to elucidate longer term effects of dietary fat saturation on glucose homeostasis. This trial was registered at PROSPERO as CRD42020178382.

Hop-derived Humulinones Reveal Protective Effects in in vitro Models of Hepatic Steatosis, Inflammation and Fibrosis.

Nonalcoholic fatty liver disease (NAFLD) is emerging as leading cause of liver disease worldwide. Specific pharmacologic therapy for NAFLD is a major unmet medical need. Recently, iso-alpha acids, hop-derived bitter compounds in beer, have been shown to beneficially affect NAFLD pathology. Humulinones are further hop derived bitter acids particularly found in modern styles of beer. So far, biological effects of humulinones have been unknown. Here, we investigated the effect of humulinones in in vitro models for hepatic steatosis, inflammation and fibrosis. Humulinones dose-dependently inhibited fatty acid induced lipid accumulation in primary human hepatocytes. Humulinones reduced the expression of fatty acid uptake transporter CD36 and key enzymes of (de novo) lipid synthesis. Conversely, humulinones increased the expression of FABP1, CPT1 and ACOX1, indicative for increased lipid combustion. Furthermore, humulinones ameliorated steatosis induced pro-inflammatory gene expression. Furthermore, humulinones significantly reduced the expression of pro-inflammatory and pro-fibrogenic factors in control as well as lipopolysaccharide treated activated hepatic stellate cells, which play a key role in hepatic fibrosis. In conclusion, humulinones beneficially affect different pathophysiological steps of NAFLD. Our data suggest humulinones as promising therapeutic agents for the prevention and treatment of NAFLD.

Geometrical isomerization of arachidonic acid during lipid peroxidation interferes with ferroptosis.

Geometrical mono-trans isomers of arachidonic acid (mtAA) are endogenous products of free radical-induced cis-trans double bond isomerization occurring to natural fatty acids during cell metabolism, including lipid peroxidation (LPO). Very little is known about the functional roles of mtAA and in general on the effects of mono-trans isomers of polyunsaturated fatty acids (mtPUFA) in various types of programmed cell death, including ferroptosis. Using HT1080 and MEF cell cultures, supplemented with 20 µM PUFA (i.e., AA, EPA or DHA) and their mtPUFA congeners, ferroptosis occurred in the presence of RSL3 (a direct inhibitor of glutathione peroxidase 4) only with the PUFA in their natural cis configuration, whereas mtPUFA showed an anti-ferroptotic effect. By performing the fatty acid-based membrane lipidome analyses, substantial differences emerged in the membrane fatty acid remodeling of the two different cell fates. In particular, during ferroptosis mtPUFA formation and their incorporation, together with the enrichment of SFA, occurred. This opens new perspectives in the role of the membrane composition for a ferroptotic outcome. While pre-treatment with AA promoted cell death for treatment with H2O2 and RSL3, mtAA did not. Cell death by AA supplementation was suppressed also in the presence of either ferroptosis inhibitors, such as the lipophilic antioxidant ferrostatin-1, or NADPH oxidase (NOX) inhibitors, including diphenyleneiodonium chloride and apocynin. Our results confirm a more complex scenario for ferroptosis than actually believed. While LPO processes are active, the importance of environmental lipid levels, balance among SFA, MUFA and PUFA in lipid pools and formation of mtPUFA influence the membrane phospholipid turnover, with crucial effects in the occurrence of cell death by ferroptosis.