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International Journal of Molecular... Jul 2023Cancer is a significant global public health issue and, despite advancements in detection and treatment, the prognosis remains poor. Cancer is a complex disease... (Review)
Review
Cancer is a significant global public health issue and, despite advancements in detection and treatment, the prognosis remains poor. Cancer is a complex disease characterized by various hallmarks, including dysregulation in apoptotic cell death pathways. Apoptosis is a programmed cell death process that efficiently eliminates damaged cells. Several studies have indicated the involvement of polyunsaturated fatty acids (PUFAs) in apoptosis, including omega-3 PUFAs such as alpha-linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid. However, the role of omega-6 PUFAs, such as linoleic acid, gamma-linolenic acid, and arachidonic acid, in apoptosis is controversial, with some studies supporting their activation of apoptosis and others suggesting inhibition. These PUFAs are essential fatty acids, and Western populations today have a high consumption rate of omega-6 to omega-3 PUFAs. This review focuses on presenting the diverse molecular mechanisms evidence in both in vitro and in vivo models, to help clarify the controversial involvement of omega-3 and omega-6 PUFAs in apoptosis mechanisms in cancer.
Topics: Humans; Fatty Acids, Unsaturated; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Docosahexaenoic Acids; Apoptosis; Neoplasms
PubMed: 37511450
DOI: 10.3390/ijms241411691 -
BMC Microbiology Nov 2023Infantile cholestasis (IC) is the most common hepatobiliary disease in infants, resulting in elevated direct bilirubin levels. Indeed, hepatointestinal circulation...
BACKGROUND
Infantile cholestasis (IC) is the most common hepatobiliary disease in infants, resulting in elevated direct bilirubin levels. Indeed, hepatointestinal circulation impacts bile acid and bilirubin metabolism. This study evaluates changes in the gut microbiota composition in children with IC and identifies abnormal metabolite profiles associated with microbial alterations.
RESULTS
The gut microbiota in the IC group exhibits the higher abundance of Veillonella, Streptococcus and Clostridium spp. (P < 0.05), compared to healthy infants (CON) group. Moreover, the abundance of Ruminococcus, Vibrio butyricum, Eubacterium coprostanogenes group, Intestinibacter, and Faecalibacterium were lower (P < 0.05). In terms of microbiota-derived metabolites, the levels of fatty acids (palmitoleic, α-linolenic, arachidonic, and linoleic) (P < 0.05) increased and the levels of amino acids decreased in IC group. Furthermore, the abundances of Ruminococcus, Eubacterium coprostanoligenes group, Intestinibacter and Butyrivibrio are positively correlated with proline, asparagine and aspartic acid, but negatively correlated with the α-linolenic acid, linoleic acid, palmitoleic acid and arachidonic acid. For analysis of the relationship between the microbiota and clinical index, it was found that the abundance of Veillonella and Streptococcus was positively correlated with serum bile acid content (P < 0.05), while APTT, PT and INR were negatively correlated with Faecalibalum and Ruminococcus (P < 0.05).
CONCLUSION
Microbiota dysbiosis happened in IC children, which also can lead to the abnormal metabolism, thus obstructing the absorption of enteral nutrition and aggravating liver cell damage. Veillonella, Ruminococcus and Butyrivibrio may be important microbiome related with IC and need further research.
Topics: Infant; Child; Humans; Gastrointestinal Microbiome; Cholestasis; Liver; Streptococcus; Bilirubin; Bile Acids and Salts
PubMed: 37980506
DOI: 10.1186/s12866-023-03115-1 -
Frontiers in Immunology 2023The modulation of immunometabolic pathways is emerging as a promising therapeutic target for immune-mediated diseases. However, the immunometabolic features of psoriatic...
Single-cell transcriptomic landscape of immunometabolism reveals intervention candidates of ascorbate and aldarate metabolism, fatty-acid degradation and PUFA metabolism of T-cell subsets in healthy controls, psoriasis and psoriatic arthritis.
INTRODUCTION
The modulation of immunometabolic pathways is emerging as a promising therapeutic target for immune-mediated diseases. However, the immunometabolic features of psoriatic disease and the potential targets for immunometabolic intervention in the different T-cell subsets involved in its pathogenesis remain unclear.
METHODS
In this study, we analyzed circulating blood single-cell data from healthy controls (HC), psoriasis (PSO), and psoriatic arthritis (PSA) patients, and revealed their metabolic features of T-cell subsets: CD4+ central memory T cells (TCMs), CD8+ effective memory T cells (TEMs), regulatory T cells (Tregs), mucosal-associated invariant T cells (MAITs ), and γδ T cells. Pearson test was performed to determine the linkages between differential metabolic and inflammatory pathways. Based on these results, we also analyzed the potential impacts of biological antibodies on differential metabolic pathways by comparing the immunometabolism differences between PSA patients without and with biological treatment.
RESULTS
Our results suggest that upregulation of ascorbate and aldarate metabolism, as well as fatty acid degradation, may enhance the immune suppression of Tregs. Enhanced metabolism of alpha-linolenic acid, linoleic acid, and arachidonic acid may inhibit the pro-inflammatory functions of CD4+ TCMs and CD8+ TEMs in PSO and PSA, and protect the immune suppression of Tregs in PSA. We propose that supporting ascorbic acid and fatty acid metabolic pathways may be an adjunctive reprogramming strategy with adalimumab and etanercept therapy.
DISCUSSION
These findings not only provide insights into immunometabolism characteristics of psoriatic disease, but also offer preliminary options for the auxiliary treatment of psoriasis.
Topics: Humans; Arthritis, Psoriatic; Transcriptome; Psoriasis; T-Lymphocyte Subsets; Ascorbic Acid
PubMed: 37492568
DOI: 10.3389/fimmu.2023.1179877 -
Galen Medical Journal 2023Overweight and obesity are the most critical risk factors for chronic diseases. The quality of dietary fatty acids as one of the factors affecting fat accumulation has...
BACKGROUND
Overweight and obesity are the most critical risk factors for chronic diseases. The quality of dietary fatty acids as one of the factors affecting fat accumulation has received little attention. This study investigates the association between dietary linoleic acid (LA) and alpha-linolenic acid (ALA) with body fat indices in a sample of healthy Iranian adults.
MATERIALS AND METHODS
In this cohort-based cross-sectional study, 3,195 individuals aged 20 to 60 who participated in the Shiraz University of Medical Science Employees Health Cohort study were included. Dietary intake was assessed using a validated 118-item Food Frequency Questionnaire (FFQ), and body composition was assessed by the bioelectrical impedance analysis method. Multiple linear regression adjusted for relevant confounders was used to determine the associations.
RESULTS
Mean dietary intake of LA was 14.20 ± 7.01 mg/day for men and 13.90 ± 6.71 mg/day for women. Additionally, the daily intake of ALA was 0.18 ± 0.18 mg/day in men and 0.17 ± 0.19 mg/day in women. Dietary intake of ALA for men had an inversely significant association with body fat mass (BFM) (β: -0.585, 95% CI: -1.137, -0.032, P=0.038), percentage of body fat (PBF) (β: -0.537, 95% CI: -0.945, -0.129, P=0.010), Visceral Fat Area (VFA) (β: -2.998, 95% CI: -5.695, -0.302, P=0.029), and Waist to Hip Ratio (WHR) (β: -0.689, 95% CI: -1.339, -0.040, P=0.038).
CONCLUSION
Higher dietary ALA intake was associated with lower BFM, BFP, VAF, and WHR in men. The present study confirms that ALA intake should be considered a preventive treatment to improve body composition. However, further research is recommended in this regard.
PubMed: 38774859
DOI: 10.31661/gmj.v12i.3023 -
Synthetic and Systems Biotechnology Sep 2023γ-Linolenic acid-enriched galactosyldiacylglycerols (GDGs-GLA), as the natural form of γ-linolenic acid in microalgae, have a range of functional activities, including... (Review)
Review
γ-Linolenic acid-enriched galactosyldiacylglycerols (GDGs-GLA), as the natural form of γ-linolenic acid in microalgae, have a range of functional activities, including anti-inflammatory, antioxidant, and anti-allergic properties. The low abundance of microalgae and the structural stereoselectivity complexity impede microalgae extraction or chemical synthesis, resulting in a lack of supply of GDGs-GLA with a growing demand. At present, there is a growing interest in engineering oleaginous yeasts for mass production of GDGs-GLA based on their ability to utilize a variety of hydrophobic substrates and a high metabolic flux toward fatty acid and lipid (triacylglycerol, TAG) production. Here, we first introduce the GDGs-GLA biosynthetic pathway in microalgae and challenges in the engineering of the native host. Subsequently, we describe in detail the applications of oleaginous yeasts with as the representative for GDGs-GLA biosynthesis, including the development of synthetic biology parts, gene editing tools, and metabolic engineering of lipid biosynthesis. Finally, we discuss the development trend of GDGs-GLA biosynthesis in .
PubMed: 37692201
DOI: 10.1016/j.synbio.2023.06.007 -
Metabolites Sep 2023Epidemiological evidence regarding the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on inflammatory bowel disease (IBD) is conflicting....
Epidemiological evidence regarding the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on inflammatory bowel disease (IBD) is conflicting. Additionally, little evidence exists regarding the effects of specific omega-3 components on IBD risk. We applied two-sample Mendelian randomization (MR) to disentangle the effects of omega-3 PUFAs (including total omega-3, α-linolenic acid, eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA)) on the risk of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Our findings indicated that genetically predicted increased EPA concentrations were associated with decreased risk of IBD (odds ratio 0.78 (95% CI 0.63-0.98)). This effect was found to be mediated through lower levels of linoleic acid and histidine metabolites. However, we found limited evidence to support the effects of total omega-3, α-linolenic acid, and DHA on the risks of IBD. In the () region, robust colocalization evidence was observed, suggesting the primary role of the gene in mediating the effects of omega-3 PUFAs on IBD. Therefore, the present MR study highlights EPA as the predominant active component of omega-3 fatty acids in relation to decreased risk of IBD, potentially via its interaction with linoleic acid and histidine metabolites. Additionally, the gene likely mediates the effects of omega-3 PUFAs on IBD risk.
PubMed: 37887366
DOI: 10.3390/metabo13101041 -
Nutrients Oct 2023We investigated the postpartum mental health of women who had consumed perilla oil or fish oil containing various omega-3 fatty acids for 12 weeks starting in... (Observational Study)
Observational Study Randomized Controlled Trial
Effects of Varied Omega-3 Fatty Acid Supplementation on Postpartum Mental Health and the Association between Prenatal Erythrocyte Omega-3 Fatty Acid Levels and Postpartum Mental Health.
We investigated the postpartum mental health of women who had consumed perilla oil or fish oil containing various omega-3 fatty acids for 12 weeks starting in mid-pregnancy. The association between fatty acids in maternal erythrocytes and mental health risk factors was also examined. Healthy Japanese primiparas in mid-pregnancy (gestational weeks 18-25) were randomly divided into two groups and consumed approximately 2.0 g/day of omega-3 fatty acids in either perilla oil (the ALA dose was 2.4 g/day) or fish oil (the EPA + DHA dose was 1.7 g/day) for 12 weeks. Maternal mental health was assessed using the Edinburgh Postnatal Depression Scale (EPDS) as the primary measure and the Mother-to-Infant Bonding Scale (MIBS) as the secondary measure. Data from an observational study were used as a historical control. Maternal blood, cord blood, and colostrum samples were collected for fatty acid composition analysis. In addition, completers of the observational studies were enrolled in a case-control study, wherein logistic regression analysis was performed to examine the association between maternal fatty acids and EPDS score. The proportion of participants with a high EPDS score (≥9) was significantly lower in the perilla oil group (12.0%, = 0.044) but not in the fish oil group (22.3%, = 0.882) compared with the historical control (21.6%), while the proportions between the former groups also tended to be lower ( = 0.059). No marked effect of omega-3 fatty acid intake was observed from the MIBS results. In the case-control study of the historical control, high levels of α-linolenic acid in maternal erythrocytes were associated with an EPDS score of <9 (odds ratio of 0.23, 95% confidence interval: 0.06, 0.84, = 0.018 for trend). The results of this study suggest that consumption of α-linolenic acid during pregnancy may stabilize postpartum mental health.
Topics: Female; Humans; Pregnancy; alpha-Linolenic Acid; Case-Control Studies; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Erythrocytes; Fatty Acids; Fatty Acids, Omega-3; Fish Oils; Mental Health; Postpartum Period; Vitamins
PubMed: 37892462
DOI: 10.3390/nu15204388 -
Advances in Nutrition (Bethesda, Md.) Nov 2023Overweight and obesity are highly prevalent worldwide and are associated with cardiovascular disease (CVD) risk factors, including systematic inflammation, dyslipidemia,... (Meta-Analysis)
Meta-Analysis Review
Effect of Alpha-Linolenic Acid Supplementation on Cardiovascular Disease Risk Profile in Individuals with Obesity or Overweight: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Overweight and obesity are highly prevalent worldwide and are associated with cardiovascular disease (CVD) risk factors, including systematic inflammation, dyslipidemia, and hypertension. Alpha-linolenic acid (ALA) is a plant-based essential polyunsaturated fatty acid associated with reduced CVD risks. This systematic review and meta-analysis aimed to investigate the effects of supplementation with ALA compared with the placebo on CVD risk factors in people with obesity or overweight (International Prospective Register of Systematic Reviews Registration No. CRD42023429563). This review included studies with adults using oral supplementation or food or combined interventions containing vegetable sources of ALA. All studies were randomly assigned trials with parallel or crossover designs. The Cochrane Collaboration tool was used for assessing the risk of bias (Version 1). PubMed, Web of Science, Embase, and Cochrane library databases were searched from inception to April 2023. Nineteen eligible randomized controlled trials, including 1183 participants, were included in the meta-analysis. Compared with placebo, dietary ALA supplementation significantly reduced C-reactive protein concentration (standardized mean difference [SMD] = -0.38 mg/L; 95% confidence interval [CI]: -0.72, -0.04), tumor necrosis factor-α concentration (SMD = -0.45 pg/mL; 95% CI: -0.73, -0.17), triglyceride in serum (SMD = -4.41 mg/dL; 95% CI: -5.99, -2.82), and systolic blood pressure (SMD = -0.37 mm Hg; 95% CI: -0.66, -0.08); but led to a significant increase in low-density lipoprotein cholesterol concentrations (SMD = 1.32 mg/dL; 95% CI: 0.05, 2.59). ALA supplementation had no significant effect on interleukin-6, diastolic blood pressure, total cholesterol, or high-density lipoprotein cholesterol (all P ≥ 0.05). Subgroup analysis revealed that ALA supplementation at a dose of ≥3 g/d from flaxseed and flaxseed oil had a more prominent effect on improving CVD risk profiles, particularly where the intervention duration was ≥12 wk and where the baseline CVD profile was poor.
Topics: Adult; Humans; Cardiovascular Diseases; alpha-Linolenic Acid; Overweight; Randomized Controlled Trials as Topic; Cholesterol, HDL; Obesity; Dietary Supplements
PubMed: 37778442
DOI: 10.1016/j.advnut.2023.09.010 -
Gut Pathogens Jul 2023Women suffer from various distress and disturbances after menopause, including osteoporosis, a risk factor associated with multiple diseases. Altered gut microbiota has...
BACKGROUND
Women suffer from various distress and disturbances after menopause, including osteoporosis, a risk factor associated with multiple diseases. Altered gut microbiota has been implicated in postmenopausal osteoporosis. In this study, to understand gut microbiota signatures and fecal metabolite changes in postmenopausal women with osteoporosis, 108 postmenopausal women were recruited for intestinal microbiota and fecal metabolite detection. Among these participants, 98 patients, who met the inclusion criteria, were divided into postmenopausal osteoporosis (PMO) and non-postmenopausal osteoporosis (non-PMO) groups based on bone mineral density (BMD). The compositions of gut bacteria and fungi were examined by 16 S rRNA gene sequencing and ITS sequencing, respectively. Meanwhile, fecal metabolites were analyzed using liquid chromatography coupled with mass spectrometry (LC-MS).
RESULTS
We found that bacterial α-diversity and β-diversity were significantly altered in PMO compared to non-PMO patients. Interestingly, fungi composition showed larger changes, and the differences in β-diversity were more significant between PMO and non-PMO patients. Metabolomics analysis revealed that fecal metabolites, such as levulinic acid, N-Acetylneuraminic acid, and the corresponding signaling pathways were also changed significantly, especially in the alpha-Linolenic acid metabolism and selenocompound metabolism. The screened differential bacteria, fungi, and metabolites closely correlated with clinical findings between these two groups, for example, the bacterial genus, Fusobacterium, the fungal genus, Devriesia, and the metabolite, L-pipecolic acid, were significantly associated with BMD.
CONCLUSIONS
Our findings indicated that there were remarkable changes in gut bacteria, fungi, and fecal metabolites in postmenopausal women, and such changes were notably correlated with patients' BMD and clinical findings. These correlations provide novel insights into the mechanism of PMO development, potential early diagnostic indicators, and new therapeutic approaches to improve bone health in postmenopausal women.
PubMed: 37415173
DOI: 10.1186/s13099-023-00553-0