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International Journal of Molecular... Aug 2023Gastric cancer (GC) typically carries a poor prognosis as it is often diagnosed at a late stage. Altered metabolism has been found to impact cancer outcomes and affect...
Gastric cancer (GC) typically carries a poor prognosis as it is often diagnosed at a late stage. Altered metabolism has been found to impact cancer outcomes and affect patients' quality of life, and the role of metabolites in gastric cancer prognosis has not been sufficiently understood. We aimed to establish a prognostic prediction model for GC patients based on a metabolism-associated signature and identify the unique role of metabolites in the prognosis of GC. Thus, we conducted untargeted metabolomics to detect the plasma metabolites of 218 patients with gastric adenocarcinoma and explored the metabolites related to the survival of patients with gastric cancer. Firstly, we divided patients into two groups based on the cutoff value of the abundance of each of the 60 metabolites and compared the differences using Kaplan-Meier (K-M) survival analysis. As a result, 23 metabolites associated with gastric cancer survival were identified. To establish a risk score model, we performed LASSO regression and Cox regression analysis on the 60 metabolites and identified 8 metabolites as an independent prognostic factor. Furthermore, a nomogram incorporating clinical parameters and the metabolic signature was constructed to help individualize outcome predictions. The results of the ROC curve and nomogram plot showed good predictive performance of metabolic risk features. Finally, we performed pathway analysis on the 24 metabolites identified in the two parts, and the results indicated that purine metabolism and arachidonic acid metabolism play important roles in gastric cancer prognosis. Our study highlights the important role of metabolites in the progression of gastric cancer and newly identified metabolites could be potential biomarkers or therapeutic targets for gastric cancer patients.
Topics: Humans; Stomach Neoplasms; Prognosis; Quality of Life; Nomograms
PubMed: 37628957
DOI: 10.3390/ijms241612774 -
Life (Basel, Switzerland) Jul 2023Certain limitations exist for animals to modify fatty acid changes. Besides the role of arachidonic acid (AA), docosahexaenoic acid (DHA) and other 20-carbon long-chain... (Review)
Review
Certain limitations exist for animals to modify fatty acid changes. Besides the role of arachidonic acid (AA), docosahexaenoic acid (DHA) and other 20-carbon long-chain polyunsaturated fatty acids (LCPUFAs) for the synthesis of inflammatory mediators as eicosanoids, different LCPUFAs have many other effects, including their abilities to regulate gene expression and downstream events. LCPUFAs are susceptible to autoxidation, which is prevented by the action of antioxidants in the form of enzymes like superoxide dismutases, catalases and peroxidases, as well as antioxidant compounds that protect against oxidation or repair the damage caused. Under normal conditions, the fetus needs both essential fatty acids (EFAs) and LCPUFAs, which are obtained from its mother by placental transfer. In early pregnancy, dietary derived fatty acids are accumulated in maternal adipose tissue. However, during late pregnancy, corresponding to the period of the highest fetal growth, maternal adipose tissue becomes catabolic and LCPUFAs are released into the circulation by adipose lipolytic activity. The released LCPUFAs are taken up by maternal liver to be esterified and released back to the circulation as triacylglycerides (TAGs) in very-low-density lipoprotein (VLDL) that become available to the placenta to be transferred to the fetus in the form of non-esterified fatty acids (NEFAs). An enhanced adipose tissue lipolysis is maintained around parturition and esterified LCPUFAs are diverted to mammary glands thanks to an increased activity of lipoprotein lipase for milk production. Throughout this process, LCPUFAs become available to the newborn during suckling. The important role of both DHA and AA for the development of the nervous system and for growth has motivated their dietary supplement during different postnatal stages. This has been especially important in preterm infants both because under normal conditions, the fetus acquires most of these fatty acids during late pregnancy, and because the immaturity of the enzyme systems for the synthesis of AA and DHA from their respective EFAs.
PubMed: 37629513
DOI: 10.3390/life13081656 -
Aging Cell Aug 2023"Lipid raft aging" in nerve cells represents an early event in the development of aging-related neurodegenerative diseases, such as Alzheimer's disease. Lipid rafts are...
"Lipid raft aging" in nerve cells represents an early event in the development of aging-related neurodegenerative diseases, such as Alzheimer's disease. Lipid rafts are key elements in synaptic plasticity, and their modification with aging alters interactions and distribution of signaling molecules, such as glutamate receptors and ion channels involved in memory formation, eventually leading to cognitive decline. In the present study, we have analyzed, in vivo, the effects of dietary supplementation of n-3 LCPUFA on the lipid structure, membrane microviscosity, domain organization, and partitioning of ionotropic and metabotropic glutamate receptors in hippocampal lipid raffs in female mice. The results revealed several lipid signatures of "lipid rafts aging" in old mice fed control diets, consisting in depletion of n-3 LCPUFA, membrane unsaturation, along with increased levels of saturates, plasmalogens, and sterol esters, as well as altered lipid relevant indexes. These changes were paralleled by increased microviscosity and changes in the raft/non-raft (R/NR) distribution of AMPA-R and mGluR5. Administration of the n-3 LCPUFA diet caused the partial reversion of fatty acid alterations found in aged mice and returned membrane microviscosity to values found in young animals. Paralleling these findings, lipid rafts accumulated mGluR5, NMDA-R, and ASIC2, and increased their R/NR proportions, which collectively indicate changes in synaptic plasticity. Unexpectedly, this diet also modified the lipidome and dimension of lipid rafts, as well as the domain redistribution of glutamate receptors and acid-sensing ion channels involved in hippocampal synaptic plasticity, likely modulating functionality of lipid rafts in memory formation and reluctance to age-associated cognitive decline.
Topics: Female; Mice; Animals; Fatty Acids; Fatty Acids, Unsaturated; Hippocampus; Membrane Microdomains; Diet
PubMed: 37254617
DOI: 10.1111/acel.13867 -
Frontiers in Oncology 2024Arachidonic acid (AA) is a crucial polyunsaturated fatty acid in the human body, metabolized through the pathways of COX, LOX, and cytochrome P450 oxidase to generate... (Review)
Review
Arachidonic acid (AA) is a crucial polyunsaturated fatty acid in the human body, metabolized through the pathways of COX, LOX, and cytochrome P450 oxidase to generate various metabolites. Recent studies have indicated that AA and its metabolites play significant regulatory roles in the onset and progression of ovarian cancer. This article examines the recent research advancements on the correlation between AA metabolites and ovarian cancer, both domestically and internationally, suggesting their potential use as biological markers for early diagnosis, targeted therapy, and prognosis monitoring.
PubMed: 38764576
DOI: 10.3389/fonc.2024.1381894 -
Frontiers in Veterinary Science 2023Classical swine fever (CSF) is an infectious disease caused by Classical swine fever virus (CSFV), which is characterized by depression, high fever, extensive skin...
Classical swine fever (CSF) is an infectious disease caused by Classical swine fever virus (CSFV), which is characterized by depression, high fever, extensive skin bleeding, leukopenia, anorexia, alternating constipation, and diarrhea. Hemorrhagic infarction of the spleen is the main characteristic pathological change following CSFV infection. Large-scale outbreaks of CSF are rare in China and are mainly distributed regionally. The clinical symptoms of CSF are not obvious, and show variation from typical to atypical symptoms, which makes diagnosis based on clinical symptoms and pathology challenging. In recent years, the incidence of CSF-immunized pig farms in China has increased and new CSFV gene subtypes have appeared, posing new challenges to the prevention and control of CSF in China. Changes in metabolites caused by viral infection reflect the pathogenic process. Metabonomics can reveal the trace metabolites of organisms; however, plasma metabonomics of CSFV-infected pigs have rarely been investigated. Therefore, we used an established pig CSFV infection model to study changes in plasma metabolites. The results showed significant differences in forty-five plasma metabolites at different time periods after CSFV infection in pigs, with an increase in twenty-five metabolites and a decrease in twenty metabolites. These changed metabolites were mainly attributed to the tricarboxylic acid cycle, amino acid cycle, sugar metabolism, and fat metabolism. Thirteen metabolic pathways changed significantly in CSFV-infected pigs, including tricarboxylic acid cycle, inositol phosphate metabolism, glycine, serine and threonine metabolism,lysine degradation, alanine, aspartate and glutamic acid metabolism, pantothenate and CoA biosynthesis, β-alanine metabolism, lysine degradation, arginine and proline metabolism, glycerolipid metabolism, phenylalanine metabolism, arachidonic acid metabolism, linoleic acid metabolism. Among these, changes in fatty acid biosynthesis and metabolism occurred at all time periods post-infection. These results indicate that CSFV infection in pigs could seriously alter metabolic pathways.
PubMed: 38130437
DOI: 10.3389/fvets.2023.1171750 -
Molecular Medicine Reports Oct 2023Endometriosis is highly dependent on angiogenesis and lymphangiogenesis. Prostaglandin E2, an arachidonic acid metabolite, has been shown to promote the formation of new...
Endometriosis is highly dependent on angiogenesis and lymphangiogenesis. Prostaglandin E2, an arachidonic acid metabolite, has been shown to promote the formation of new blood and lymphatic vessels. However, the role of another arachidonic acid metabolite, thromboxane A (TXA) in angiogenesis and lymphangiogenesis during endometriosis remains largely unexplored. Using a murine model of ectopic endometrial transplantation, fragments from the endometrium of WT donor mice were transplanted into the peritoneal walls of recipient WT mice (WT→WT), resulting in an increase in both the area and density of blood and lymphatic vessels. Upon transplantation of endometrial tissue from thromboxane prostanoid (TP) receptor (TXA receptor)‑deficient (TP) mice into TP mice (TP→TP), an increase in implant growth, angiogenesis, and lymphangiogenesis were observed along with upregulation of pro‑angiogenic and lymphangiogenic factors, including vascular endothelial growth factors (VEGFs). Similar results were obtained using a thromboxane synthase (TXS) inhibitor in WT→WT mice. Furthermore, TP→TP mice had a higher number of F4/80 cells than that of WT→WT mice, with increased expression of genes related to the anti‑inflammatory macrophage phenotype in endometrial lesions. In cultured bone marrow (BM)‑derived macrophages, the levels of VEGF‑A, VEGF‑C, and VEGF‑D decreased in a TP‑dependent manner. Furthermore, TP signaling affected the polarization of cultured BM‑derived macrophages to the anti‑inflammatory phenotype. These findings imply that inhibition of TP signaling promotes endometrial implant growth and neovascularization.
Topics: Animals; Female; Mice; Arachidonic Acid; Dinoprostone; Endometriosis; Neovascularization, Pathologic; Prostaglandins; Thromboxanes; Receptors, Thromboxane A2, Prostaglandin H2
PubMed: 37654213
DOI: 10.3892/mmr.2023.13079 -
Clinical Nutrition (Edinburgh, Scotland) May 2024Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIM
Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown positive effects on inflammation-related morbidities, but the molecular mechanisms underlying these effects are not fully elucidated. This study aimed to determine associations between DHA, AA, and inflammation-related proteins during the neonatal period in extremely preterm infants.
METHODS
A retrospective exploratory study of infants (n = 183) born below 28 weeks gestation from the Mega Donna Mega trial, a randomized multicenter trial designed to study the effect of DHA and AA on retinopathy of prematurity. Serial serum samples were collected after birth until postnatal day 100 (median 7 samples per infant) and analyzed for phospholipid fatty acids and proteins using targeted proteomics covering 538 proteins. Associations over time between LCPUFAs and proteins were explored using mixed effect modeling with splines, including an interaction term for time, and adjusted for gestational age, sex, and center.
RESULTS
On postnatal day one, 55 proteins correlated with DHA levels and 10 proteins with AA levels. Five proteins were related to both fatty acids, all with a positive correlation. Over the first 100 days after birth, we identified 57 proteins to be associated with DHA and/or AA. Of these proteins, 41 (72%) related to inflammation. Thirty-eight proteins were associated with both fatty acids and the overall direction of association did not differ between DHA and AA, indicating that both LCPUFAs similarly contribute to up- and down-regulation of the preterm neonate inflammatory proteome. Primary examples of this were the inflammation-modulating cytokines IL-6 and CCL7, both being negatively related to levels of DHA and AA in the postnatal period.
CONCLUSIONS
This study supports postnatal non-antagonistic and potentially synergistic effects of DHA and AA on the inflammation proteome in preterm infants, indicating that supplementation with both fatty acids may contribute to limiting the disease burden in this vulnerable population.
CLINICAL REGISTRATION NUMBER
ClinicalTrials.gov (NCT03201588).
Topics: Humans; Docosahexaenoic Acids; Arachidonic Acid; Infant, Extremely Premature; Infant, Newborn; Female; Retrospective Studies; Male; Inflammation; Proteome
PubMed: 38603973
DOI: 10.1016/j.clnu.2024.03.031 -
Heliyon Apr 2024Endocannabinoids (eCBs) exert considerable influence over energy metabolism, lipid metabolism, and glucose metabolism within the human body. Among the most biologically...
Endocannabinoids (eCBs) exert considerable influence over energy metabolism, lipid metabolism, and glucose metabolism within the human body. Among the most biologically active cannabinoids identified thus far are 2-arachidonoylglycerol (2-AG), arachidonoyl ethanolamide (AEA), 1-stearoylglycerol (1-SRG), and stearoyl ethanolamide (SEA), which are derived from arachidonic acid (AA) and stearic acid (SA). However, despite the unique in bioactivities exhibited by eCBs, their determination in plasma has been hindered by the lack of sensitive analytical methods. The aim of this study was to develop and validate a highly sensitive and rapid method using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for accurate measurement of AEA, SEA, 2-AG, 1-SRG, AA, and SA levels in human plasma samples. Sample preparation involved a protein precipitation method and a methyl -butyl ether liquid-liquid extraction method. Chromatographic separation was accomplished by utilizing an ACQUITY UPLC BEH C column with a mobile phase of acetonitrile containing 0.1% formic acid and water containing 0.1% formic acid, flowing at a rate of 0.35 mL/min. AA-d, 2-AG-d, and AEA-d were selected as deuterated internal standards. The analytes were determined with MRM in both positive and negative ion mode. The lower limit of quantification ranged from 0.1 to 400 ng/mL, and the correlation coefficient (R) was >0.99. Inter-day and intra-day precision exhibited values of 0.55-13.29% and 0.62%-13.90%, respectively. Recovery and matrix effect were within the range of 77.7%-109.7%, and 90.0%-113.5%, respectively. Stability tests confirmed the acceptability of all analytes. To demonstrate the effectiveness of the approach, it was implemented to assess and compare plasma samples from healthy volunteers (n = 49) and individuals with non-alcoholic fatty liver disease (NAFLD) (n = 62). The study revealed significant differences in AEA, SEA, AA, and SA levels between the two groups.
PubMed: 38560270
DOI: 10.1016/j.heliyon.2024.e28467 -
Alternative Therapies in Health and... Oct 2023Acute stroke is characterized by rapid progression, high mortality, and disability rates, making it a significant focus in clinical research. Brain-protective agents,... (Review)
Review
BACKGROUND
Acute stroke is characterized by rapid progression, high mortality, and disability rates, making it a significant focus in clinical research. Brain-protective agents, such as butylphthalide and edaravone, have emerged as important therapeutic options for acute stroke.
OBJECTIVE
This study aimed to explore how butylphthalide and edaravone promote healing in acute stroke, drawing on relevant data, literature, clinical experience, and personal concepts.
DESIGN
The study design involves a narrative review, which comprehensively explores the pathogenesis of stroke by referencing relevant data and literature. Clinical experience and personal insights were incorporated to provide a holistic understanding. The primary focus was analyzing the mechanisms through which butylphthalide and edaravone facilitate healing in stroke patients.
RESULTS
The review revealed that butylphthalide exhibited multiple beneficial effects, including the protection of mitochondria, reduction of the inflammatory response, enhancement of microcirculation, decrease in blood-brain barrier permeability, and improving nerve cell function. On the other hand, edaravone demonstrated its efficacy by reducing oxidative stress response, inhibiting inflammatory response, and regulating the metabolism of arachidonic acid and apoptosis. These findings highlight the distinct mechanisms through which butylphthalide and edaravone contribute to the healing process in patients with stroke.
CONCLUSIONS
This study highlights the positive impact of butylphthalide and edaravone on the therapeutic effect and short-term prognosis in acute stroke patients. The findings provide valuable guidance for future research and enhance our understanding of these drugs' mechanisms, offering the potential for improved stroke management and patient outcomes.
Topics: Humans; Edaravone; Sodium Chloride; Antipyrine; Stroke; Treatment Outcome
PubMed: 37499159
DOI: No ID Found -
Archives of Biochemistry and Biophysics Dec 2023Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver disorder affecting a significant part of the global population. This study aimed to...
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver disorder affecting a significant part of the global population. This study aimed to investigate the potential therapeutic effects of α-lipoic acid (α-LA) on the inflammatory response during simple steatosis development and progression into steatohepatitis. The study used the MASLD model in male Wistar rats that were fed a standard diet or a high-fat diet (HFD) for 8 weeks. Throughout the entire experiment, half of the animals received α-LA supplementation. The hepatic activity of pro-inflammatory n-6 and anti-inflammatory n-3 polyunsaturated fatty acid (PUFA) pathways and the concentration of arachidonic acid (AA) in selected lipid fractions were determined by the gas-liquid chromatography (GLC). The hepatic expression of proteins from inflammatory pathway was measured by the Western blot technique. The level of eicosanoids, cytokines and chemokines was assessed by the ELISA or multiplex assay kits. The results showed that α-LA supplementation attenuated the activity of n-6 PUFA pathway in FFA and DAG and increased the activity of n-3 PUFA pathway in PL, TAG and DAG. In addition, the administration of α-LA decreased the concentration of AA in DAG and FFA, indicating its potential protective effect on the deterioration of simple hepatic steatosis. The supplementation of α-LA also increased the expression of COX-1 and COX-2 with the lack of significant changes in prostaglandins profile. We observed an increase in the expression of 12/15-LOX, which was reflected in an increase in lipoxin A4 (LXA4) level. A decrease in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines was also noticed in the liver of rats treated with HFD and α-LA. Our observations confirm that α-LA treatment has potential protective effects on inflammation development in the MASLD model. We believe that α-LA has a preventive impact when it comes to the progression of simple steatosis lesions to steatohepatitis.
Topics: Rats; Male; Animals; Thioctic Acid; Diet, High-Fat; Rats, Wistar; Fatty Liver; Liver; Inflammation; Anti-Inflammatory Agents; Cytokines
PubMed: 37926405
DOI: 10.1016/j.abb.2023.109811