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The use of omega-3 fatty acids (omega-3 FA) in the treatment of atopic dermatitis (AD) is an area of ongoing research. Some studies suggest that dietary supplementation with omega-3 FA can help manage symptoms of AD by reducing lesion severity, skin inflammation, dryness and itching, while others show no significant beneficial effect. The aim of this study was to evaluate the effect of omega-3 FA from fish oil in combination with gamma-linolenic acid (GLA) from blackcurrant seed oil in children with AD. This is a longitudinal, prospective, randomized, triple blind, placebo-controlled parallel clinical trial. The study was conducted during the 2-year period throughout autumn, winter, and spring, avoiding the summer when AD usually improves. Children were randomized to receive the active study product (Mega Kid®) containing a specific blend of omega-3 and omega-6 fatty acids or placebo. The primary outcomes were changes in severity of AD measured using SCORing Atopic Dermatitis (SCORAD), patient-oriented SCORAD (PO-SCORAD) and the difference in topical corticosteroid (TCS) use. The secondary outcomes were changes in itch intensity, sleep quality and Family Dermatology Life Quality Index (FDLQI). Data were analyzed for 52 children (26 in the intervention group and 26 in the placebo group). In children receiving the active product, intention-to-treat analysis showed that after 4 months of treatment, there was a significant decrease in the SCORAD index (from median 42 to 25, p < 0.001) and the use of topical corticosteroids (from median 30 to 10 mg/month, p < 0.001), but also significant improvements in itch, sleep quality, and overall quality of life. Omega-3 fatty acids in combination with GLA and vitamin D may decrease symptoms and were associated with an improvement clinical picture of AD in children. Therefore, we can conclude that supplementation with this specific combination could be considered a safe and effective intervention that may significantly reduce the severity of AD in pediatric patients.
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Dermatitis Atópica , Suplementos Dietéticos , Ácidos Grasos Omega-3 , Calidad de Vida , Ácido gammalinolénico , Humanos , Dermatitis Atópica/tratamiento farmacológico , Femenino , Masculino , Ácidos Grasos Omega-3/administración & dosificación , Niño , Preescolar , Resultado del Tratamiento , Estudios Prospectivos , Ácido gammalinolénico/administración & dosificación , Ácido gammalinolénico/uso terapéutico , Índice de Severidad de la Enfermedad , Estudios Longitudinales , Prurito/tratamiento farmacológicoRESUMEN
This study presents a comprehensive strategy for the selection and optimization of solvent systems in countercurrent chromatography (CCC) for the effective separation of compounds. With a focus on traditional organic solvent systems, the research introduces a "sweet space" strategy that merges intuitive understanding with mathematical accuracy, addressing the significant challenges in solvent system selection, a critical bottleneck in the widespread application of CCC. By employing a combination of volume ratios and graphical representations, including both regular and trirectangular tetrahedron models, the proposed approach facilitates a more inclusive and user-friendly strategy for solvent system selection. This study demonstrates the potential of the proposed strategy through the successful separation of gamma-linolenic acid, oleic acid, and linoleic acid from borage oil, highlighting the strategy's effectiveness and practical applicability in CCC separations.
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Distribución en Contracorriente , Aceites de Plantas , Solventes , Solventes/química , Aceites de Plantas/química , Aceites de Plantas/aislamiento & purificación , Ácidos Grasos Insaturados/química , Ácidos Grasos Insaturados/aislamiento & purificación , Ácido gammalinolénicoRESUMEN
Background: Gamma-linolenic acid (GLA) is found in animals and plants that play a role in brain function and metabolism. Objective: This study aimed to investigate the analgesic effects of GLA on peripheral formalin injection. Methods: Wistar rats were randomly assigned to four groups: Sham, formalin, formalin/GLA 100 mg/kg, and formalin/GLA 150 mg/kg. The Formalin test was utilized to create a pain model. A tissue sample was prepared from the spinal cords of rats to measure oxidative stress parameters and pro-inflammatory cytokines. Furthermore, the authors analyzed the expression of c-Fos protein in the spinal cords. Results: Our findings demonstrate that GLA has a reliable pain-relieving effect in the formalin test. GLA 100 increased superoxide dismutase (SOD) (P<0.05), glutathione (GSH) (P<0.001), and catalase (CAT) (P<0.05), and decreased the levels of c-Fos (P<0.001), interleukin-1 beta (IL-1ß) (P<0.001), tumour necrosis factor-alpha (TNF-α) (P<0.001), and malondialdehyde (MDA) (P<0.001) in the spinal cord. Also GLA 150 increased SOD (P<0.05), GSH (P<0.001), and CAT (P<0.05) and decreased the levels of c-Fos (P<0.001), IL-1ß (P<0.001), TNF-α (P<0.001), and MDA (P<0.001) in the spinal cord. Conclusion: The findings have validated the antinociceptive impact of GLA and hinted towards its immunomodulatory influence in the formalin test.
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The primary goal of the investigation was to analyse the anti-inflammatory and antioxidant properties of Gamma-linolenic acid (GLA) on rats with indomethacin (IND)-induced gastric ulcers. Thirty rats were divided into five groups: Control, IND (50 mg/kg, p.o.), IND pretreated with GLA 100 mg/kg (p.o. for 14 d), IND pretreated with GLA 150 mg/kg (p.o. for 14 d) and IND pretreated with omeprazole (20 mg/kg, p.o. for 14 d). The stomach tissues were examined to calculate the ulcer index and pH and analyse biochemical markers (prostaglandin E2 (PGE2), cyclooxygenase 1 (COX1), TNF-1, IL-6 and intercellular adhesion molecule-1 (ICAM1)) and oxidative stress parameters (malondialdehyde: (MDA), superoxide dismutase (SOD), glutathione (GSH) and CAT (catalase)) as well as undergo histopathological assessment. GLA 100 and 150 mg/kg showed a protective effect against IND-induced gastric damage. It reduced levels of COX1, TNF-1, IL-6 and ICAM and increased PGE2 levels. GLA also normalised antioxidant function by modulating MDA, SOD, GSH and CAT. GLA intervention protects against IND-induced gastric ulcers by restoring oxidant/antioxidant balance and reducing inflammation.
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Antioxidantes , Dinoprostona , Indometacina , Estrés Oxidativo , Ratas Wistar , Úlcera Gástrica , Ácido gammalinolénico , Animales , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & control , Úlcera Gástrica/tratamiento farmacológico , Indometacina/efectos adversos , Antioxidantes/farmacología , Ratas , Estrés Oxidativo/efectos de los fármacos , Ácido gammalinolénico/farmacología , Masculino , Dinoprostona/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Interleucina-6/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Superóxido Dismutasa/metabolismo , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Glutatión/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Antiinflamatorios/farmacología , Ciclooxigenasa 1/metabolismo , Malondialdehído/metabolismo , Omeprazol/farmacologíaRESUMEN
Cunninghamella elegans NRRL-1393 is an oleaginous fungus able to synthesize and accumulate unsaturated fatty acids, amongst which the bioactive gamma-linolenic acid (GLA) has potential anti-cancer activities. C. elegans was cultured in shake-flask nitrogen-limited media with either glycerol or glucose (both at ≈60 g/L) employed as the sole substrate. The assimilation rate of both substrates was similar, as the total biomass production reached 13.0-13.5 g/L, c. 350 h after inoculation (for both instances, c. 27-29 g/L of substrate were consumed). Lipid production was slightly higher on glycerol-based media, compared to the growth on glucose (≈8.4 g/L vs. ≈7.0 g/L). Lipids from C. elegans grown on glycerol, containing c. 9.5% w/w of GLA, were transformed into fatty acid lithium salts (FALS), and their effects were assessed on both human normal and cancerous cell lines. The FALS exhibited cytotoxic effects within a 48 h interval with an IC50 of about 60 µg/mL. Additionally, a suppression of migration was shown, as a significant elevation of oxidative stress levels, and the induction of cell death. Elementary differences between normal and cancer cells were not shown, indicating a generic mode of action; however, oxidative stress level augmentation may increase susceptibility to anticancer drugs, improving chemotherapy effectiveness.
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BACKGROUND: Evening primrose oil (EPO), extracted from the seeds of Oenothera biennis, has gained attention for its therapeutic effects in various inflammatory conditions. METHOD: We performed a systematic search in multiple databases and defined the inclusion criteria based on the following PICOs: P: Patients with a form of inflammatory condition, I: EPO, C: Placebo or other therapeutic interventions, O: changes in inflammatory markers or patients' symptoms; S: randomized controlled trials. The quality of the RCTs was evaluated using Cochrane's RoB tool. RESULTS: Several conditions were investigated in the literature. In rheumatoid arthritis, mixed results were observed, with some studies reporting significant improvements in symptoms while others found no significant impact. EPO showed some results in diabetes mellitus, atopic eczema, menopausal hot flashes, and mastalgia. However, it did not demonstrate effectiveness in chronic hand dermatitis, tardive dyskinesia, psoriatic arthritis, cystic fibrosis, hepatitis B, premenstrual syndrome, contact lens-associated dry eyes, acne vulgaris, breast cyst, pre-eclampsia, psoriasis, or primary Sjogren's syndrome. Some results were reported from multiple sclerosis after EPO consumption. Studies in healthy volunteers indicated no significant effect of EPO on epidermal atrophy, nevertheless, positive effects on the skin regarding hydration and barrier function were achieved. CONCLUSION: Some evidence regarding the potential benefits of EPO in inflammatory disorders were reported however caution is due to the limitations of the current survey. Overall, contemporary literature is highly heterogeneous and fails to provide strong recommendations regarding the efficacy of EPO on inflammatory disorders. Further high-quality studies are necessitated to draw more definite conclusions and establish O. biennis oil effectiveness as an assuring treatment option in alleviating inflammatory conditions.
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Oenothera biennis , Aceites de Plantas , Humanos , Aceites de Plantas/farmacología , Aceites de Plantas/uso terapéutico , Ácido gammalinolénico/uso terapéutico , Ácido gammalinolénico/farmacología , Inflamación/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Ácidos Linoleicos/farmacología , Ácidos Linoleicos/uso terapéuticoRESUMEN
OBJECTIVES: Current medications for diabetic neuropathy (DN) recommended by the American Diabetes Association and American Academy of Neurology do not address the pathologic process of denervation among patients with DN, because ancillary treatments, such as reactive oxygen scavengers, may be needed. The purpose of this work was to summarize the available evidence about the efficacy and safety of alpha lipoic acid (ALA) and gamma linolenic acid (GLA) in the management of DN. METHODS: Using the search terms [(alpha lipoic acid or ALA or thioctic acid or thioctacid) or (gamma linolenic acid or GLA)] AND [(diabetes or diabetes mellitus) AND (polyneuropathy or neuropathy or sensorimotor polyneuropathy or radiculopathy)], 11 studies were included in this review and combined meta-analysis. RESULTS: Eight of the 11 articles (73%) reported significant benefit of ALA vs placebo. In the meta-analysis, the Total Symptom Score (TSS) for ALA 600 mg/day (ALA600) was 1.05 points lower (standard mean difference [SMD] -1.05, 95% confidence interval [CI] -2.07 to -0.04, p=0.04, I2=98.18%) compared with control at the end of the study. In the network meta-analysis, ALA600 (SMD -1.68, 95% CI -2.8 to -0.6) and GLA (SMD -2.39, 95% CI -4.3 to -0.5) had significantly lower TSSs compared with placebo. Moreover, GLA had the highest probability of being the best (52.7%) for improving DN symptoms. In all studies, most adverse events include gastrointestinal disturbances. In terms of tolerability, no differences were detected between ALA and control groups. CONCLUSION: ALA and GLA appear to be safe and efficacious biofactors for improvement of DN symptoms.
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Neuropatías Diabéticas , Ácido Tióctico , Ácido gammalinolénico , Humanos , Ácido Tióctico/uso terapéutico , Neuropatías Diabéticas/tratamiento farmacológico , Ácido gammalinolénico/uso terapéutico , Ácido gammalinolénico/administración & dosificación , Metaanálisis en Red , Adulto , Resultado del Tratamiento , Antioxidantes/uso terapéutico , Antioxidantes/administración & dosificaciónRESUMEN
BACKGROUND: The development of rosacea is suggested to be closely associated with lipid metabolism, inflammation, and anxiety/depression. Gamma linolenic acid (GLA) is a key factor participating in lipid metabolism, which is also confirmed to regulate the inflammatory response. However, the associations of serum GLA levels with rosacea severity and psychological status still remain unclear. OBJECTIVE AND LIMITATIONS OF THE STUDY: The present study aimed to investigate the associations of gamma linolenic acid (GLA), a key factor participating in lipid metabolism and the inflammatory response, with rosacea severity and psychological status. The present study still had some limitations. First, this study is a cross-sectional study and does not provide longitudinal evidence about the relationship between GLA and rosacea; Second, the cohort in this study is also relatively small, and a larger cohort is needed in further investigation to reveal the potential role of lipid metabolism in the pathogenesis of rosacea. METHODS: A total of 62 rosacea patients were consecutively recruited. Patient's Self-Assessment (PSA) scale and Clinician Erythema Assessment (CEA) as well as 7-item Generalized Anxiety Disorder (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9) were conducted to evaluate the degree of erythema severity and anxiety/depression, respectively. Serum GLA levels were determined by gas chromatography mass. RESULTS: Lower levels of serum GLA in rosacea patients were observed (p<0.001), and subgroup analysis revealed that patients with higher-level GLA had lower scores of PSA, CEA, GAD-7 and PHQ-9. Moreover, Spearman correlation analysis uncovered that serum GLA levels were negatively associated with PSA, CEA, GAD-7 as well and PHQ-9 scores, respectively. Linear regression model found that serum GLA levels at baseline were a predictive factor for prognosis of clinical outcomes after 1-month conventional treatment. CONCLUSION: The present study indicates that lower levels of serum GLA in rosacea patients are negatively associated with the degree of erythema and anxiety/depression status.
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Rosácea , Ácido gammalinolénico , Humanos , Ácido gammalinolénico/uso terapéutico , Depresión/etiología , Estudios Transversales , Índice de Severidad de la Enfermedad , Rosácea/complicaciones , Rosácea/psicología , Eritema/etiología , Eritema/tratamiento farmacológico , Ansiedad/etiologíaRESUMEN
Abstract Background The development of rosacea is suggested to be closely associated with lipid metabolism, inflammation, and anxiety/depression. Gamma linolenic acid (GLA) is a key factor participating in lipid metabolism, which is also confirmed to regulate the inflammatory response. However, the associations of serum GLA levels with rosacea severity and psychological status still remain unclear. Objective and limitations of the study The present study aimed to investigate the associations of gamma linolenic acid (GLA), a key factor participating in lipid metabolism and the inflammatory response, with rosacea severity and psychological status. The present study still had some limitations. First, this study is a cross-sectional study and does not provide longitudinal evidence about the relationship between GLA and rosacea; Second, the cohort in this study is also relatively small, and a larger cohort is needed in further investigation to reveal the potential role of lipid metabolism in the pathogenesis of rosacea. Methods A total of 62 rosacea patients were consecutively recruited. Patient's Self-Assessment (PSA) scale and Clinician Erythema Assessment (CEA) as well as 7-item Generalized Anxiety Disorder (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9) were conducted to evaluate the degree of erythema severity and anxiety/depression, respectively. Serum GLA levels were determined by gas chromatography mass. Results Lower levels of serum GLA in rosacea patients were observed (p < 0.001), and subgroup analysis revealed that patients with higher-level GLA had lower scores of PSA, CEA, GAD-7 and PHQ-9. Moreover, Spearman correlation analysis uncovered that serum GLA levels were negatively associated with PSA, CEA, GAD-7 as well and PHQ-9 scores, respectively. Linear regression model found that serum GLA levels at baseline were a predictive factor for prognosis of clinical outcomes after 1-month conventional treatment. Conclusion The present study indicates that lower levels of serum GLA in rosacea patients are negatively associated with the degree of erythema and anxiety/depression status.
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A major obstacle for chemotherapeutics in Glioblastoma (GB) is to reach the tumour cells due to the presence of the blood-brain barrier (BBB) and chemoresistance of anticancer drugs. The present study reports two polyunsaturated fatty acids, gamma-linolenic acid (GLA) and alpha-linolenic acid (ALA) appended nanostructured lipid carriers (NLCs) of a CNS negative chemotherapeutic drug docetaxel (DTX) for targeted delivery to GB. The ligand appended DTX-NLCs demonstrated particle size < 160 nm, PDI < 0.29 and a negative surface charge. The successful linkage of GLA (41 %) and ALA (30 %) ligand conjugation to DTX- NLCs was confirmed by diminished surface amino groups on the NLCs, lower surface charge and FTIR profiling. Fluorophore labelled GLA-DTX-NLCs and ALA-DTX-NLCs permeated the in-vitro 3D BBB model with Papp values of 1.8 × 10-3 and 1.9 × 10-3 cm/s respectively. Following permeation, both formulations showed enhanced uptake by GB immortalised cells while ALA-DTX-NLCs showed higher uptake in patient-derived GB cells as evidenced in an in-vitro 3D blood brain tumour barrier (BBTB) model. Both surface functionalised formulations showed higher internalisation in GB cells as compared to bare DTX-NLCs. ALA-DTX-NLCs and GLA-DTX-NLCs showed 13.9-fold and 6.8-fold higher DTX activity respectively at 24 h as indicated by IC50 values when tested in patient-derived GB cells. ALA-DTX-NLCs displayed better efficacy than GLA-DTX-NLCs when tested against 3D tumour spheroids and patient-derived cells. These novel formulations will contribute widely to overcoming biological barriers for treating glioblastoma.
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Portadores de Fármacos , Glioblastoma , Humanos , Glioblastoma/tratamiento farmacológico , Barrera Hematoencefálica , Ligandos , Lípidos/uso terapéutico , Docetaxel , Ácidos Grasos Insaturados/uso terapéuticoRESUMEN
Cabazitaxel (CTX) is a medication used for treating metastatic prostate cancer. However, its effectiveness is majorly limited by its poor water solubility and lack of tumor targeting. In this study, three unsaturated fatty acids, GLA, ALA and DHA, were separately connected with CTX and then covalently attached to bifunctionalized dextran through a linker to produce three dual drug conjugates named dextran-GLA-CTX, dextran-ALA-CTX and dextran-DHA-CTX. The three conjugates displayed enhanced solubility of CTX in water and improved antitumor effects compared to the conventional CTX formulation. The results also confirmed that dextran-GLA-CTX exhibited the strongest antitumor activity, while dextran-DHA-CTX displayed less efficacy, as evaluated through xenografted nude mice bearing PC-3 and DU145 prostate cancer cells. Additionally, dextran-GLA-CTX showed greater inhibition of tumor growth than dextran-CTX. Moreover, the dextran-GLA-CTX conjugate was found to prolong the half-life of CTX in plasma and selectively accumulate in tumors. This study revealed that unsaturated fatty acids can enhance the antitumor activity of dextran-based conjugates grafted with CTX.
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Dextranos , Neoplasias de la Próstata , Humanos , Masculino , Ratones , Animales , Ratones Desnudos , Ácidos Grasos Insaturados/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Agua , Ácidos Docosahexaenoicos , Ácidos GrasosRESUMEN
n-3 polyunsaturated fatty acids (PUFAs) have an inhibitory effect on the development of coronary artery disease (CAD). However, whether n-6 PUFAs, dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) play a role in the development of CAD remains unclear. This study investigated the association between PUFAs and the risk of developing acute coronary syndrome (ACS) using the lipid and PUFAs data of patients who received percutaneous coronary intervention (PCI) for either non-emergent conditions (staged group) or ACS (ACS group). We retrospectively evaluated 433 patients who underwent PCI between 2014 and 2021. The patients were divided into the ACS group (n = 18) and the staged group (n = 132). The lipid and PUFA values of each patient between the two groups were compared. Moreover, to investigate the correlation between n-6 PUFA levels and ACS, the effects of confounding factors such as the use of strong statins and low-density lipoprotein cholesterol (LDL-C) levels were adjusted. The ACS group had higher n-6 PUFAs levels than the staged group (DGLA: 36.8 µg/mL vs 29.6 µg/mL; AA: 203.3 µg/mL vs 145.8 µg/mL). Furthermore, the analysis of covariance adjusted for LDL-C levels showed a significant difference between the two groups in terms of DGLA and AA levels. The n-3 PUFA levels did not significantly differ between the staged and ACS groups. Moreover, the ACS group had higher DGLA and AA levels and lower n-3 PUFAs/AA ratios than the staged group. Therefore, excess n-6 PUFAs may be a risk factor for ACS.
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Síndrome Coronario Agudo , Ácidos Grasos Omega-3 , Intervención Coronaria Percutánea , Humanos , Estudios Retrospectivos , LDL-Colesterol , Ácidos Grasos Insaturados , Ácido AraquidónicoRESUMEN
Omega-6 polyunsaturated fatty acids (ω6-PUFAs), such as γ-linolenic acid (GLA), dihomo-γ-linolenic acid (DGLA) and arachidonic acid (ARA), are indispensable nutrients for human health. Harnessing the lipogenesis pathway of Yarrowia lipolytica creates a potential platform for producing customized ω6-PUFAs. This study explored the optimal biosynthetic pathways for customized production of ω6-PUFAs in Y. lipolytica via either the Δ6 pathway from Mortierella alpina or the Δ8 pathway from Isochrysis galbana. Subsequently, the proportion of ω6-PUFAs in total fatty acids (TFAs) was effectively increased by bolstering the provision of precursors for fatty acid biosynthesis and carriers for fatty acid desaturation, as well as preventing fatty acid degradation. Finally, the proportions of GLA, DGLA and ARA synthesized by customized strains accounted for 22.58%, 46.65% and 11.30% of TFAs, and the corresponding titers reached 386.59, 832.00 and 191.76 mg/L in shake-flask fermentation, respectively. This work provides valuable insights into the production of functional ω6-PUFAs.
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Ácidos Grasos Omega-3 , Yarrowia , Humanos , Yarrowia/metabolismo , Ácidos Grasos , Ácido Araquidónico , Ácido gammalinolénico/metabolismo , Ácido 8,11,14-Eicosatrienoico/metabolismoRESUMEN
This review is about the role of arachidonic acid (ArA) in foetal and early growth and development. In 1975 and '76, we reported the preferential incorporation of ArA into the developing brain of rat pups, its conservation as a principal component in the brains of 32 mammalian species and the high proportion delivered by the human placenta for foetal nutrition, compared to its parent linoleic acid (LA). ArA is quantitatively the principal acyl component of membrane lipids from foetal red cells, mononuclear cells, astrocytes, endothelium, and placenta. Functionally, we present evidence that ArA, but not DHA, relaxes the foetal mesenteric arteries. The placenta biomagnifies ArA, doubling the proportion of the maternal level in cord blood. The proportions of ArA and its allies (di-homo-gamma-linolenic acid (DGLA), adrenic acid and ω6 docosapentaenoic acid) are similar or higher than the total of ω3 fatty acids in human milk, maintaining the abundant supply to the developing infant. Despite the evidence of the importance of ArA, the European Food Standard Agency, in 2014 rejected the joint FAO and WHO recommendation on the inclusion of ArA in infant formula, although they recommended DHA. The almost universal dominance of ArA in the membrane phosphoglycerides during human organogenesis and prenatal growth suggests that the importance of ArA and its allies in reproductive biology needs to be re-evaluated urgently.
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Ácidos Docosahexaenoicos , Ácido Linoleico , Embarazo , Femenino , Humanos , Animales , Ratas , Ácido Araquidónico/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ácido Linoleico/metabolismo , Fórmulas Infantiles , Glicerofosfolípidos , Mamíferos/metabolismoRESUMEN
Background: Herbal medicine could be effective at treating various illnesses. Hysteroscopy can be an effective method for assessing the uterus in terms of anatomical, physiological and pathological anomalies. Objective: This study aims to evaluate the effect of evening primrose oil (EPO) on cervical preparation in women candidates for hysteroscopy. Materials and Methods: This study was a double-blind, randomized controlled clinical trial including 160 women candidates for diagnostic hysteroscopy who were referred to Alzahra hospital from August 2019-March 2020. They were divided into 2 groups. Group A received 100 mg EPO as a soft gel capsule 6 hr before the hysterectomy in the posterior vaginal fornix. Group B received a placebo. After receiving the treatment, primary and secondary outcomes were evaluated in the groups. Results: The average Hegar size in the EPO group was larger than in the control group (p < 0.001 for both). Also, the need for mechanical dilation, the time taken until the first resistance and the time of dilatation completion in the EPO group were significantly less than in the placebo group (p < 0.008 for all). There was also greater ease of dilatation in the EPO group. Side effects such as uterine rupture, false passage, cervical rupture, allergic reaction, abdominal pain, nausea, diarrhea, headache and increase of bowel movements were not reported in any cases. Conclusion: Based on the findings of the present study, EPO is effective for cervical preparation in women undergoing hysteroscopy.
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Background: Colorectal cancer (CRC) is one of the most common malignant tumors with recurrence and metastasis after surgical resection. This study aimed to identify the physiological changes after surgery and explore metabolites and metabolic pathways with potential prognostic value for CRC. Methods: An ultra-high-performance liquid chromatography Q-exactive mass spectrometry was used to profile serum metabolites from 67 CRC patients and 50 healthy volunteers. Principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis were used to distinguish the internal characteristics of data in different groups. Multivariate statistics were compiled to screen the significant metabolites and metabolic pathways. Result: A total of 180 metabolites were detected. Under the conditions of variable importance in projection >1 and p-value <0.05, 46 differentially expressed metabolites were screened for further pathway enrichment analysis. Based on the Kyoto Encyclopedia of Genes and Genomes database and Small Molecule Pathway Database, three metabolic pathways-arginine and proline metabolism, ascorbate and aldarate metabolism, and phenylalanine metabolism-were significantly altered after surgical resection and identified as associated with the removal of CRC. Notably, gamma-linolenic acid was upregulated in the CRC preoperative patients compared with those in healthy volunteers but returned to healthy levels after surgery. Conclusion: Through serum-based metabolomics, our study demonstrated the differential metabolic characteristics in CRC patients after surgery compared with those before surgery. Our results suggested that metabonomic analysis may be a powerful method for exploring physiological alterations in CRC patients after surgery as well as a useful tool for identifying candidate biomarkers and monitoring disease recurrence.
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γ-Linolenic acid (GLA) is an essential n-6 polyunsaturated fatty acid (PUFA) that has received considerable attention in human and animal feed. GLA is used in many nutritional and medicinal applications, such as the treatment of cancer, inflammatory disorders, and diabetes. Currently, plant seed is the primary dietary source of GLA that is not enough to utilize on an industrial scale. To generate a sustainable novel source of GLA, the gene of delta-6 desaturase, one of the essential enzymes in the GLA production pathway, was isolated from Mucor rouxii DSM1194 and expressed in P. pastoris GS115 by pPICZC vector. The recombinant yeast expressed the GLA up to 19.2% (72 mg/g) of total fatty acids. GLA production of recombinant yeast was studied in a fermenter by oil waste for 5 days, and results detected 6.3 g/l lipid, and 103 mg/g GLA was produced in 72 h. The present study may provide an opportunity to develop an alternative host for manufacturing GLA on an industrial scale.
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Pichia , Saccharomycetales , Ácido gammalinolénico , Ácido Graso Desaturasas/genética , Ácido Graso Desaturasas/metabolismo , Ácidos Grasos/metabolismo , Pichia/genética , Pichia/metabolismo , Saccharomycetales/genética , Saccharomycetales/metabolismo , Ácido gammalinolénico/metabolismoRESUMEN
The use of polyunsaturated fatty acids in Attention-Deficit/Hyperactivity Disorder (ADHD) and developmental disorders has been gaining interest with preparations containing different dosages and combinations. Gamma-linolenic acid (GLA) is an ω-6 fatty acid of emerging interest with potential roles as an adjuvant anti-inflammatory agent that could be used with ω-3 PUFAs in the treatment of ADHD and associated symptoms. A narrative review was undertaken to examine the potential role(s) of the ω-6 fatty acid GLA. PubMed, Google Scholar, and Scopus were searched to examine the potential role(s) of the ω-6 fatty acid GLA as (1) an antioxidant and anti-inflammatory agent, (2) a synergistic nutrient when combined with ω-3 PUFAs, and (3) a potential etiological factor in ADHD and its treatment. The results show that GLA exerts anti-inflammatory effects by increasing dihomo-gamma-linolenic acid in immune cells. ω-3 PUFAs, such as EPA and DHA, are often co-administered with GLA because these ω-3 PUFAs may prevent the accumulation of serum arachidonic acid in response to GLA administration without limiting the storage of DGLA in immune cells. The administration of ω-3 PUFAs alone might not be sufficient to effectively treat patients with ADHD and developmental disorders. Overall studies point towards a combination of EPA and DHA with GLA in a 9:3:1 ratio appearing to be associated with ADHD symptom improvement. A combination of PUFAs may lead to better outcomes.
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Trastorno por Déficit de Atención con Hiperactividad , Ácidos Grasos Omega-3 , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Suplementos Dietéticos , Ácidos Grasos Omega-6 , Ácidos Grasos Insaturados , HumanosRESUMEN
BACKGROUND: Children born extremely preterm disproportionately experience sequelae of preterm birth compared to those born at later gestational ages, including higher prevalence of autism spectrum disorder (ASD) and associated behaviors. AIM: Explore effects of combined dietary docosahexaenoic acid, eicosapentaenoic acid, gamma-linolenic acid, and oleic acid (omega 3-6-9) on caregiver-reported behavior and sleep in toddlers born at ≤29 weeks' gestation who were exhibiting symptoms commonly seen with ASD. STUDY DESIGN: 90-day randomized (1:1), double blinded, placebo-controlled trial. SUBJECTS: Thirty-one children aged 18-38 months received omega 3-6-9 (n = 15) or canola oil placebo (n = 16). OUTCOME MEASURES: Mixed effects regression analyses followed intent to treat and explored treatment effects on measures of caregiver-reported behavior (Child Behavior Checklist 1.5-5, Toddler Behavior Assessment Questionnaire - Short Form, Vineland Adaptive Behavior Scales, 2nd Edition) and sleep (Children's Sleep Habits Questionnaire, Brief Infant Sleep Questionnaire). RESULTS: Twenty-nine of 31 (94%; ntx = 13, nplacebo = 16) children randomized had data available for at least one outcome measure, 27 (87%; ntx = 12, nplacebo = 15) had complete outcome data. Children randomized to omega 3-6-9 experienced a medium magnitude benefit of supplementation on anxious and depressed behaviors (ΔDifference = -1.27, d = -0.58, p = 0.049) and internalizing behaviors (ΔDifference = -3.41, d = -0.68, p = 0.05); and a large magnitude benefit on interpersonal relationship adaptive behaviors (ΔDifference = 7.50, d = 0.83, p = 0.01), compared to placebo. No effects were observed on other aspects of behavior or sleep. CONCLUSIONS: Findings provide preliminary support for further exploration of omega 3-6-9 during toddlerhood to improve socioemotional outcomes among children born preterm, especially for those showing early symptoms commonly seen with ASD. Results need to be replicated in a larger sample. TRIAL REGISTRATION: Registered with ClinicalTrials.gov: NCT01683565.
Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Ácidos Grasos Omega-3 , Nacimiento Prematuro , Trastorno del Espectro Autista/tratamiento farmacológico , Preescolar , Suplementos Dietéticos , Ácidos Docosahexaenoicos , Método Doble Ciego , Ácidos Grasos Omega-3/uso terapéutico , Femenino , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , SueñoRESUMEN
Gamma-linolenic acid (GLA), a natural fatty acid obtained from oils of various vegetables and seeds, has been demonstrated as an anticancer agent. In this work, we investigated the anticancer effects of GLA on breast cancer BT-474 cells. GLA at 30 µM, a concentration reportedly within the range of circulating concentrations in clinical studies, caused apoptotic cell death. GLA caused an elevation in mitochondrial Ca2+ level and a decrease in mitochondrial membrane potential. GLA treatment depleted cyclopiazonic acid (CPA)-sensitive Ca2+ store and triggered substantial Ca2+ influx. Intracellular Ca2+ release triggered by GLA was suppressed by 3 µM xestospongin C (XeC, IP3 receptor-channel blocker) and 100 µM ryanodine (ryanodine receptor-channel blocker), suggesting that the Ca2+ release was via IP3 receptor-channel and ryanodine receptor-channel. Increased expressions of p-eIF2α and CHOP were observed in GLA-treated cells, suggesting GLA-treated cells had increased expressions of p-eIF2α and CHOP, which suggest endoplasmic reticulum (ER) stress. In addition, GLA elicited increased production of reactive oxygen species. Taken together, our results suggest a basal level of GLA induced apoptotic cell death by causing Ca2+ overload, mitochondrial dysfunction, Ca2+ store depletion, ER stress, and oxidative stress. This is the first report to show that GLA caused Ca2+ store depletion and ER stress. GLA-induced Ca2+ store depletion resulted from opening of IP3 receptor-channel and ryanodine receptor-channel.