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Journal of the American Heart... Jun 2024A lower serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio (EPA/AA) level correlates with cardiovascular events. Nevertheless, elevated serum EPA levels...
BACKGROUND
A lower serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio (EPA/AA) level correlates with cardiovascular events. Nevertheless, elevated serum EPA levels increase the risk of new-onset atrial fibrillation (AF) in older patients. The relationship between the EPA/AA and outcomes post-AF ablation remains unclear. This study investigated the impact of the EPA/AA on AF recurrence and cardiovascular events after AF ablation in older patients.
METHODS AND RESULTS
This retrospective cohort study examined consecutive patients with AF aged ≥65 years who underwent a first-time AF ablation. We compared the 3-year AF recurrence and 5-year major adverse cardiovascular event (MACE) rates between patients divided into high and low EPA/AA levels defined as above and below the median EPA/AA value before ablation. MACE was defined as heart failure hospitalizations, strokes, coronary artery disease, major bleeding, and cardiovascular death. Among the 673 included patients, the median EPA/AA value was 0.35. Compared with the low EPA/AA group, the high EPA/AA group had a significantly higher cumulative incidence of AF recurrence (39.3% versus 27.6%; log-rank =0.004) and lower cumulative incidence of MACE (13.8% versus 25.5%, log-rank =0.021). A high EPA/AA level was determined as an independent predictor of AF recurrence (hazard ratio [HR], 1.75 95% CI, 1.24-2.49; =0.002) and MACE (HR, 0.60 [95% CI, 0.36-0.99]; =0.046).
CONCLUSIONS
The EPA/AA was associated with AF recurrence and MACE after ablation in patients with AF aged ≥65 years.
PubMed: 38879457
DOI: 10.1161/JAHA.123.033969 -
The American Journal of Clinical... Jun 2024A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences expression of FADS1, which controls synthesis of n-6 highly unsaturated...
Fatty acid desaturase insertion-deletion polymorphism rs66698963 predicts colorectal polyp prevention by the n-3 fatty acid eicosapentaenoic acid: A secondary analysis of the seAFOod polyp prevention trial.
BACKGROUND
A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences expression of FADS1, which controls synthesis of n-6 highly unsaturated fatty acid (HUFA) arachidonic acid (AA). The anti-inflammatory activity of the n-3 HUFA eicosapentaenoic acid (EPA) may be explained by competition with AA for pro-inflammatory lipid mediator synthesis. A precision medicine approach based on stratification by FADS Indel genotype could identify individuals, who benefit from greatest disease risk reduction by n-3 HUFAs.
OBJECTIVE
We tested the hypothesis that the FADS insertion (I) allele predicts colorectal polyp risk reduction in a secondary analysis of the randomized, placebo-controlled, 2 x 2 factorial seAFOod polyp prevention trial of EPA 2000 mg daily and aspirin 300 mg daily for 12 months (ISRCTN05926847).
METHODS
Participant Indel genotype was determined by PCR blind to trial outcomes. Colorectal polyp outcomes were included in negative binomial (polyp number) and logistic (polyp detection rate [PDR; percentage with one or more polyps]) regression models comparing each active intervention versus placebo. Presence of at least one Indel I allele and an interaction term (I allele x active intervention) were co-variates.
RESULTS
In 528 participants with colonoscopy and FADS Indel data, EPA use irrespective of Indel genotype, was not associated with reduced colorectal polyp number (incidence rate ratio [IRR] 0.92, 95% confidence interval 0.74, 1.16), mirroring original seAFOod trial analysis. However, presence of at least one I allele identified EPA users with a significant reduction in colorectal polyp number (IRR 0.50 [0.28, 0.90]), unlike aspirin, for which there was no interaction. Similar findings were obtained for the PDR.
CONCLUSIONS
The FADS Indel I allele identified individuals, who displayed colorectal polyp prevention by EPA with a similar effect size to aspirin. Assessment of rs66698963 as a biomarker of therapeutic response to n-3 HUFAs in other populations and healthcare settings is warranted.
TRIAL REGISTRATION
The seAFOod polyp prevention trial and STOP-ADENOMA study are registered with https://www.isrctn.com as ISRCTN05926847.
PubMed: 38879016
DOI: 10.1016/j.ajcnut.2024.06.004 -
Biomedicine & Pharmacotherapy =... Jun 2024Myocardial reperfusion injury occurs when blood flow is restored after ischemia, an essential process to salvage ischemic tissue. However, this phenomenon is intricate,... (Review)
Review
Myocardial reperfusion injury occurs when blood flow is restored after ischemia, an essential process to salvage ischemic tissue. However, this phenomenon is intricate, characterized by various harmful effects. Tissue damage in ischemia-reperfusion injury arises from various factors, including the production of reactive oxygen species, the sequestration of proinflammatory immune cells in ischemic tissues, the induction of endoplasmic reticulum stress, and the occurrence of postischemic capillary no-reflow. Secretory phospholipase A2 (sPLA2) plays a crucial role in the eicosanoid pathway by releasing free arachidonic acid from membrane phospholipids' sn-2 position. This liberated arachidonic acid serves as a substrate for various eicosanoid biosynthetic enzymes, including cyclooxygenases, lipoxygenases, and cytochromes P450, ultimately resulting in inflammation and an elevated risk of reperfusion injury. Therefore, the activation of sPLA2 directly correlates with the heightened and accelerated damage observed in myocardial ischemia-reperfusion injury (MIRI). Presently, clinical trials are in progress for medications aimed at sPLA2, presenting promising avenues for intervention. Cardiolipin (CL) plays a crucial role in maintaining mitochondrial function, and its alteration is closely linked to mitochondrial dysfunction observed in MIRI. This paper provides a critical analysis of CL modifications concerning mitochondrial dysfunction in MIRI, along with its associated molecular mechanisms. Additionally, it delves into various pharmacological approaches to prevent or alleviate MIRI, whether by directly targeting mitochondrial CL or through indirect means.
PubMed: 38878685
DOI: 10.1016/j.biopha.2024.116936 -
Parasites & Vectors Jun 2024Toxoplasma gondii is an intracellular protozoan parasite that is widely distributed in humans and warm-blooded animals. T. gondii chronic infections can cause...
BACKGROUND
Toxoplasma gondii is an intracellular protozoan parasite that is widely distributed in humans and warm-blooded animals. T. gondii chronic infections can cause toxoplasmic encephalopathy, adverse pregnancy, and male reproductive disorders. In male reproduction, the main function of the testis is to provide a stable place for spermatogenesis and immunological protection. The disorders affecting testis tissue encompass abnormalities in the germ cell cycle, spermatogenic retardation, or complete cessation of sperm development. However, the mechanisms of interaction between T. gondii and the reproductive system is unclear. The aims were to study the expression levels of genes related to spermatogenesis, following T. gondii infection, in mouse testicular tissue.
METHODS
RNA-seq sequencing was carried out on mouse testicular tissues from mice infected or uninfected with the T. gondii type II Prugniaud (PRU) strain and validated in combination with real-time quantitative PCR and immunofluorescence assays.
RESULTS
The results showed that there were 250 significant differentially expressed genes (DEGs) (P < 0.05, |logfold change| ≧ 1). Bioinformatics analysis showed that 101 DEGs were annotated to the 1696 gene ontology (GO) term. While there was a higher number of DEGs in the biological process classification as a whole, the GO enrichment revealed a significant presence of DEGs in the cellular component classification. The Arhgap18 and Syne1 genes undergo regulatory changes following T. gondii infection, and both were involved in shaping the cytoskeleton of the blood-testis barrier (BTB). The number of DEGs enriched in the MAPK signaling pathway, the ERK1/2 signaling pathway, and the JNK signaling pathway were significant. The PTGDS gene is located in the Arachidonic acid metabolism pathway, which plays an important role in the formation and maintenance of BTB in the testis. The expression of PTGDS is downregulated subsequent to T. gondii infection, potentially exerting deleterious effects on the integrity of the BTB and the spermatogenic microenvironment within the testes.
CONCLUSIONS
Overall, our research provides in-depth insights into how chronic T. gondii infection might affect testicular tissue and potentially impact male fertility. These findings offer a new perspective on the impact of T. gondii infection on the male reproductive system.
Topics: Animals; Male; Mice; Testis; Toxoplasma; Transcriptome; Toxoplasmosis, Animal; Spermatogenesis; Gene Expression Profiling; Chronic Disease; Computational Biology
PubMed: 38858789
DOI: 10.1186/s13071-024-06247-z -
ACS Omega Jun 2024Arachidonic acid (ARA) was shown to possess safe and effective schistosomicidal impact on larval and adult and in vitro and in vivo in laboratory rodents and in...
Arachidonic acid (ARA) was shown to possess safe and effective schistosomicidal impact on larval and adult and in vitro and in vivo in laboratory rodents and in children residing in low and high endemicity regions. We herein examine mechanisms underlying ARA schistosomicidal potential over two experiments, using in each pool a minimum of 50 adult male, female, or mixed-sex freshly recovered, ex vivo . Worms incubated in fetal calf serum-free medium were exposed to 0 or 10 mM ARA for 1 h at 37 °C and immediately processed for preparation of surface membrane and whole worm body homogenate extracts. Mixed-sex worms were additionally used for evaluating the impact of ARA exposure on the visualization of outer membrane cholesterol, sphingomyelin (SM), and ceramide in immunofluorescence assays. Following assessment of protein content, extracts of intact and ARA-treated worms were examined and compared for SM content, neutral sphingomyelinase activity, reactive oxygen species levels, and caspase 3/7 activity. Arachidonic acid principally led to perturbation of the organization, integrity, and SM content of the outer membrane of male and female worms and additionally impacted female parasites via stimulating neutral sphingomyelinase activity and oxidative stress. Arachidonic powerful action on female worms combined with its previously documented ovocidal activities supports its use as safe and effective therapy against schistosomiasis, provided implementation of the sorely needed and long waited-for chemical synthesis.
PubMed: 38854551
DOI: 10.1021/acsomega.3c09906 -
Ecotoxicology and Environmental Safety Jun 2024In this study, a six-month pot experiment was conducted to explore the effects of nanoparticles (NPs), including CeO, TiO and SiO NPs at 200 and 800 mg/kg, on the...
In this study, a six-month pot experiment was conducted to explore the effects of nanoparticles (NPs), including CeO, TiO and SiO NPs at 200 and 800 mg/kg, on the growth and quality of model medicinal plant Salvia miltiorrhiza. A control group was implemented without the application of NPs. Results showed that NPs had no significant effect on root biomass. Treatment with 200 mg/kg of SiO NPs significantly increased the total tanshinone content by 44.07 %, while 200 mg/kg of CeO NPs were conducive to a 22.34 % increase in salvianolic acid B content. Exposure to CeO NPs induced a substantial rise in the MDA content in leaves (176.25 % and 329.15 % under low and high concentration exposure, respectively), resulting in pronounced oxidative stress. However, TiO and SiO NPs did not evoke a robust response from the antioxidant system. Besides, high doses of CeO NP-amended soil led to reduced nitrogen, phosphorus and potassium contents. Furthermore, the NP amendment disturbed the carbon and nitrogen metabolism in the plant rhizosphere and reshaped the rhizosphere microbial community structure. The application of CeO and TiO NPs promoted the accumulation of metabolites with antioxidant functions, such as D-altrose, trehalose, arachidonic acid and ergosterol. NPs displayed a notable suppressive effect on pathogenic fungi (Fusarium and Gibberella) in the rhizosphere, while enriching beneficial taxa with disease resistance, heavy metal antagonism and plant growth promotion ability (Lysobacter, Streptomycetaceae, Bacillaceae and Hannaella). Correlation analysis indicated the involvement of rhizosphere microorganisms in plant adaptation to NP amendments. NPs regulate plant growth and quality by altering soil properties, rhizosphere microbial community structure, and influencing plant and rhizosphere microbe metabolism. These findings were beneficial to deepening the understanding of the mechanism by which NPs affect medicinal plants.
PubMed: 38850694
DOI: 10.1016/j.ecoenv.2024.116552 -
Chinese Medicine Jun 2024Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disease worldwide. Si-Wu-Tang (SWT), a traditional Chinese medicine decoction...
BACKGROUND
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disease worldwide. Si-Wu-Tang (SWT), a traditional Chinese medicine decoction has shown therapeutic effects on various liver diseases. However, the hepatoprotective effects and underlying mechanism of SWT on MAFLD remain unclear.
METHODS
First, a methionine-choline-deficient (MCD) diet-fed mice model was used and lipidomic analysis and transcriptomic analysis were performed. The contents of total iron ions, ferrous ions, and lipid peroxidation were detected and Prussian blue staining was performed to confirm the protective effects of SWT against ferroptosis. Finally, chemical characterization and network pharmacological analysis were employed to identify the potential active ingredients.
RESULTS
Serological and hepatic histopathological findings indicated SWT's discernible therapeutic impact on MCD diet-induced MAFLD. Lipidomic analysis revealed that SWT improved intrahepatic lipid accumulation by inhibiting TG synthesis and promoting TG transport. Transcriptomic analysis suggested that SWT ameliorated abnormal FA metabolism by inhibiting FA synthesis and promoting FA β-oxidation. Then, ferroptosis phenotype experiments revealed that SWT could effectively impede hepatocyte ferroptosis, which was induced by long-chain acyl-CoA synthetase 4 (ACSL4)-mediated esterification of arachidonic acid (AA). Finally, chemical characterization and network pharmacological analysis identified that paeoniflorin and other active ingredients might be responsible for the regulative effects against ferroptosis and MAFLD.
CONCLUSION
In conclusion, our study revealed the intricate mechanism through which SWT improved MCD diet-induced MAFLD by targeting FA metabolism and ferroptosis in hepatocytes, thus offering a novel therapeutic approach for the treatment of MAFLD and its complications.
PubMed: 38844978
DOI: 10.1186/s13020-024-00953-7 -
Scientific Reports Jun 2024Osteosarcoma is a primary malignant tumor that commonly affects children and adolescents, with a poor prognosis. The existence of tumor heterogeneity leads to different...
Osteosarcoma is a primary malignant tumor that commonly affects children and adolescents, with a poor prognosis. The existence of tumor heterogeneity leads to different molecular subtypes and survival outcomes. Recently, lipid metabolism has been identified as a critical characteristic of cancer. Therefore, our study aims to identify osteosarcoma's lipid metabolism molecular subtype and develop a signature for survival outcome prediction. Four multicenter cohorts-TARGET-OS, GSE21257, GSE39058, and GSE16091-were amalgamated into a unified Meta-Cohort. Through consensus clustering, novel molecular subtypes within Meta-Cohort patients were delineated. Subsequent feature selection processes, encompassing analyses of differentially expressed genes between subtypes, univariate Cox analysis, and StepAIC, were employed to pinpoint biomarkers related to lipid metabolism in TARGET-OS. We selected the most effective algorithm for constructing a Lipid Metabolism-Related Signature (LMRS) by utilizing four machine-learning algorithms reconfigured into ten unique combinations. This selection was based on achieving the highest concordance index (C-index) in the test cohort of GSE21257, GSE39058, and GSE16091. We identified two distinct lipid metabolism molecular subtypes in osteosarcoma patients, C1 and C2, with significantly different survival rates. C1 is characterized by increased cholesterol, fatty acid synthesis, and ketone metabolism. In contrast, C2 focuses on steroid hormone biosynthesis, arachidonic acid, and glycerolipid and linoleic acid metabolism. Feature selection in the TARGET-OS identified 12 lipid metabolism genes, leading to a model predicting osteosarcoma patient survival. The LMRS, based on the 12 identified genes, consistently accurately predicted prognosis across TARGET-OS, testing cohorts, and Meta-Cohort. Incorporating 12 published signatures, LMRS showed robust and significantly superior predictive capability. Our results offer a promising tool to enhance the clinical management of osteosarcoma, potentially leading to improved clinical outcomes.
Topics: Osteosarcoma; Humans; Machine Learning; Lipid Metabolism; Prognosis; Bone Neoplasms; Biomarkers, Tumor; Female; Male; Gene Expression Regulation, Neoplastic; Adolescent; Gene Expression Profiling; Child
PubMed: 38839983
DOI: 10.1038/s41598-024-63736-y -
Drug Metabolism and Disposition: the... Jun 2024This research aimed to clarify the impacts of cannflavin-C on angiotensin II (Ang II)-induced cardiac hypertrophy and their potential role in modulating cytochrome P450...
This research aimed to clarify the impacts of cannflavin-C on angiotensin II (Ang II)-induced cardiac hypertrophy and their potential role in modulating cytochrome P450 1B1 (CYP1B1) and arachidonic acid (AA) metabolites. Currently there is no evidence to suggest that cannflavin-C; a prenylated flavonoid, has any significant effects on the heart or cardiac hypertrophy. The metabolism of arachidonic acid (AA) into midchain hydroxyeicosatetraenoic acids (HETEs), facilitated by CYP1B1 enzyme, plays a role in the development of cardiac hypertrophy which is marked by enlarged cardiac cells. Adult human ventricular cardiomyocytes cell line (AC16) were cultured and exposed to cannflavin-C in the presence and absence of Ang II. The assessment of mRNA expression pertaining to cardiac hypertrophic markers and CYPs was conducted via real-time polymerase chain reaction (PCR) while the quantification of CYPs protein levels was carried out through western blot analysis. Ang II induced hypertrophic markers myosin heavy chain (β/α-MHC), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) and increased cell surface area, while cannflavin-C mitigated these effects. Gene and protein expression analysis revealed that cannflavin-C downregulated CYP1B1 gene expression, protein level as well as the enzyme activity assessed by 7-methoxyresorufin O-deethylase (MROD). Arachidonic acid metabolites analysis, using LC-MS/MS, demonstrated that Ang II increased midchain (R/S)-HETEs concentrations, which were attenuated by cannflavin-C. This study provides novel insights into the potential of cannflavin-C in modulating arachidonic acid metabolites and attenuating Ang II-induced cardiac hypertrophy, highlighting the importance of this compound as potential therapeutic agents for cardiac hypertrophy. This study demonstrates that cannflavin-C offers protection against cellular hypertrophy induced by Ang II. The significance of this research lies in its novel discovery, which elucidates a mechanistic pathway involving the inhibition of CYP 1B1 by cannflavin-C. This discovery opens up new avenues for leveraging this compound in the treatment of heart failure.
PubMed: 38839111
DOI: 10.1124/dmd.124.001705 -
Mikrochimica Acta Jun 2024A trendsetting direct competitive-based biosensing tool has been developed and implemented for the determination of the polyunsaturated fatty acid arachidonic acid...
A trendsetting direct competitive-based biosensing tool has been developed and implemented for the determination of the polyunsaturated fatty acid arachidonic acid (ARA), a highly significant biological regulator with decisive roles in viral infections. The designed methodology involves a competitive reaction between the target endogenous ARA and a biotin-ARA competitor for the recognition sites of anti-ARA antibodies covalently attached to the surface of carboxylic acid-coated magnetic microbeads (HOOC-MµBs), followed by the enzymatic label of the biotin-ARA residues with streptavidin-horseradish peroxidase (Strep-HRP) conjugate. The resulting bioconjugates were magnetically trapped onto the sensing surface of disposable screen-printed carbon transducers (SPCEs) to monitor the extent of the biorecognition reaction through amperometry. The operational functioning of the exhaustively optimized and characterized immunosensing bioplatform was highly convenient for the quantitative determination of ARA in serum samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2-) and respiratory syncytial virus (RSV)-infected individuals in a rapid, affordable, trustful, and sensitive manner.
Topics: Humans; Arachidonic Acid; COVID-19; Biosensing Techniques; SARS-CoV-2; Horseradish Peroxidase; Respiratory Syncytial Viruses; Immunoassay; Streptavidin; Biotin; Limit of Detection
PubMed: 38834823
DOI: 10.1007/s00604-024-06440-y