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Frontiers in Nutrition 2021A good nutritional status is important for maintaining normal body function and preventing or mitigating the dysfunction induced by internal or external factors.... (Review)
Review
A good nutritional status is important for maintaining normal body function and preventing or mitigating the dysfunction induced by internal or external factors. Nutritional deficiencies often result in impaired function, and, conversely, intakes at recommended levels can resume or further enhance body functions. An increasing number of studies are revealing that diet and nutrition are critical not only for physiology and body composition, but also have significant effects on mood and mental well-being. In particular, Western dietary habits have been the object of several research studies focusing on the relationship between nutrition and mental health. This review aims to summarize the current knowledge about the relationship between the intake of specific micro- and macronutrients, including eicosapentaenoic acid, docosahexaenoic acid, alpha-tocopherol, magnesium and folic acid, and mental health, with particular reference to their beneficial effect on stress, sleep disorders, anxiety, mild cognitive impairment, as well as on neuropsychiatric disorders, all significantly affecting the quality of life of an increasing number of people. Overall data support a positive role for the nutrients mentioned above in the preservation of normal brain function and mental well-being, also through the control of neuroinflammation, and encourage their integration in a well-balanced and varied diet, accompanied by a healthy lifestyle. This strategy is of particular importance when considering the global human aging and that the brain suffers significantly from the life-long impact of stress factors.
PubMed: 33763446
DOI: 10.3389/fnut.2021.656290 -
International Journal of Molecular... Jul 2020Ferroptosis is an iron-dependent form of cell death characterized by intracellular lipid peroxide accumulation and redox imbalance. Ferroptosis shows specific biological... (Review)
Review
Ferroptosis is an iron-dependent form of cell death characterized by intracellular lipid peroxide accumulation and redox imbalance. Ferroptosis shows specific biological and morphological features when compared to the other cell death patterns. The loss of lipid peroxide repair activity by glutathione peroxidase 4 (GPX4), the presence of redox-active iron and the oxidation of polyunsaturated fatty acid (PUFA)-containing phospholipids are considered as distinct fingerprints of ferroptosis. Several pathways, including amino acid and iron metabolism, ferritinophagy, cell adhesion, p53, Keap1/Nrf2 and phospholipid biosynthesis, can modify susceptibility to ferroptosis. Through the decades, various diseases, including acute kidney injury; cancer; ischemia-reperfusion injury; and cardiovascular, neurodegenerative and hepatic disorders, have been associated with ferroptosis. In this review, we provide a comprehensive analysis of the main biological and biochemical mechanisms of ferroptosis and an overview of chemicals used as inducers and inhibitors. Then, we report the contribution of ferroptosis to the spectrum of liver diseases, acute or chronic. Finally, we discuss the use of ferroptosis as a therapeutic approach against hepatocellular carcinoma, the most common form of primary liver cancer.
Topics: Animals; Autophagy; Chemical and Drug Induced Liver Injury; Cyclohexylamines; Cysteine; Ferroptosis; Glutathione; Heme; Humans; Iron; Kelch-Like ECH-Associated Protein 1; Lipid Peroxidation; Lipoxygenase; Liver Diseases; Liver Neoplasms; Oxidative Stress; Phenylenediamines; Phospholipid Hydroperoxide Glutathione Peroxidase; Piperazines; Quinoxalines; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; Sorafenib; Spiro Compounds; Sulfasalazine; Tumor Suppressor Protein p53; alpha-Tocopherol
PubMed: 32664576
DOI: 10.3390/ijms21144908 -
Cell Jul 2021Emerging evidence indicates a fundamental role for the epigenome in immunity. Here, we mapped the epigenomic and transcriptional landscape of immunity to influenza... (Randomized Controlled Trial)
Randomized Controlled Trial
Emerging evidence indicates a fundamental role for the epigenome in immunity. Here, we mapped the epigenomic and transcriptional landscape of immunity to influenza vaccination in humans at the single-cell level. Vaccination against seasonal influenza induced persistently diminished H3K27ac in monocytes and myeloid dendritic cells (mDCs), which was associated with impaired cytokine responses to Toll-like receptor stimulation. Single-cell ATAC-seq analysis revealed an epigenomically distinct subcluster of monocytes with reduced chromatin accessibility at AP-1-targeted loci after vaccination. Similar effects were observed in response to vaccination with the AS03-adjuvanted H5N1 pandemic influenza vaccine. However, this vaccine also stimulated persistently increased chromatin accessibility at interferon response factor (IRF) loci in monocytes and mDCs. This was associated with elevated expression of antiviral genes and heightened resistance to the unrelated Zika and Dengue viruses. These results demonstrate that vaccination stimulates persistent epigenomic remodeling of the innate immune system and reveal AS03's potential as an epigenetic adjuvant.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Antigens, CD34; Antiviral Agents; Cellular Reprogramming; Chromatin; Cytokines; Drug Combinations; Epigenomics; Female; Gene Expression Regulation; Histones; Humans; Immunity; Immunity, Innate; Influenza A Virus, H5N1 Subtype; Influenza Vaccines; Interferon Type I; Male; Myeloid Cells; Polysorbates; Single-Cell Analysis; Squalene; Toll-Like Receptors; Transcription Factor AP-1; Transcription, Genetic; Transcriptome; Vaccination; Young Adult; alpha-Tocopherol
PubMed: 34174187
DOI: 10.1016/j.cell.2021.05.039 -
The EMBO Journal Jan 2023The cellular activation of the NLRP3 inflammasome is spatiotemporally orchestrated by various organelles, but whether lysosomes contribute to this process remains...
The cellular activation of the NLRP3 inflammasome is spatiotemporally orchestrated by various organelles, but whether lysosomes contribute to this process remains unclear. Here, we show the vital role of the lysosomal membrane-tethered Ragulator complex in NLRP3 inflammasome activation. Deficiency of Lamtor1, an essential component of the Ragulator complex, abrogated NLRP3 inflammasome activation in murine macrophages and human monocytic cells. Myeloid-specific Lamtor1-deficient mice showed marked attenuation of NLRP3-associated inflammatory disease severity, including LPS-induced sepsis, alum-induced peritonitis, and monosodium urate (MSU)-induced arthritis. Mechanistically, Lamtor1 interacted with both NLRP3 and histone deacetylase 6 (HDAC6). HDAC6 enhances the interaction between Lamtor1 and NLRP3, resulting in NLRP3 inflammasome activation. DL-all-rac-α-tocopherol, a synthetic form of vitamin E, inhibited the Lamtor1-HDAC6 interaction, resulting in diminished NLRP3 inflammasome activation. Further, DL-all-rac-α-tocopherol alleviated acute gouty arthritis and MSU-induced peritonitis. These results provide novel insights into the role of lysosomes in the activation of NLRP3 inflammasomes by the Ragulator complex.
Topics: Mice; Humans; Animals; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammation; Histone Deacetylase 6; alpha-Tocopherol; Uric Acid; Peritonitis; Lysosomes; Mice, Inbred C57BL
PubMed: 36444797
DOI: 10.15252/embj.2022111389 -
Cell Death & Disease Feb 2020Acetaminophen (APAP) overdose is a common cause of drug-induced acute liver failure. Although hepatocyte cell death is considered to be the critical event in...
Acetaminophen (APAP) overdose is a common cause of drug-induced acute liver failure. Although hepatocyte cell death is considered to be the critical event in APAP-induced hepatotoxicity, the underlying mechanism remains unclear. Ferroptosis is a newly discovered type of cell death that is caused by a loss of cellular redox homeostasis. As glutathione (GSH) depletion triggers APAP-induced hepatotoxicity, we investigated the role of ferroptosis in a murine model of APAP-induced acute liver failure. APAP-induced hepatotoxicity (evaluated in terms of ALT, AST, and the histopathological score), lipid peroxidation (4-HNE and MDA), and upregulation of the ferroptosis maker PTGS2 mRNA were markedly prevented by the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1). Fer-1 treatment also completely prevented mortality induced by high-dose APAP. Similarly, APAP-induced hepatotoxicity and lipid peroxidation were prevented by the iron chelator deferoxamine. Using mass spectrometry, we found that lipid peroxides derived from n-6 fatty acids, mainly arachidonic acid, were elevated by APAP, and that auto-oxidation is the predominant mechanism of APAP-derived lipid oxidation. APAP-induced hepatotoxicity was also prevented by genetic inhibition of acyl-CoA synthetase long-chain family member 4 or α-tocopherol supplementation. We found that ferroptosis is responsible for APAP-induced hepatocyte cell death. Our findings provide new insights into the mechanism of APAP-induced hepatotoxicity and suggest that ferroptosis is a potential therapeutic target for APAP-induced acute liver failure.
Topics: Acetaminophen; Animals; Antioxidants; Coenzyme A Ligases; Cyclohexylamines; Cyclooxygenase 2; Deferoxamine; Disease Models, Animal; Fatty Acids, Omega-6; Ferroptosis; Hepatocytes; Humans; Iron Chelating Agents; Lipid Peroxidation; Liver; Liver Failure, Acute; Mice, Inbred C57BL; Mice, Knockout; Oxidation-Reduction; Phenylenediamines; alpha-Tocopherol
PubMed: 32094346
DOI: 10.1038/s41419-020-2334-2 -
Nutrients Jul 2023The relationship between vitamin E intake or circulating α-tocopherol and various health outcomes is still debatable and uncertain. We conducted an umbrella review to... (Review)
Review
The relationship between vitamin E intake or circulating α-tocopherol and various health outcomes is still debatable and uncertain. We conducted an umbrella review to identify the relationships between vitamin E intake or circulating tocopherol and health outcomes by merging and recalculating earlier meta-analyses. The connections that were found to be statistically significant were then classified into different evidence levels based on values, between-study heterogeneity, prediction intervals, and small study effects. We finally included 32 eligible meta-analyses with four vitamin E sources and 64 unique health outcomes. Only the association between circulating α-tocopherol and wheeze or asthma in children was substantiated by consistent evidence. Suggestive evidence was suggested for seven results on endothelial function (supplemental vitamin E): serum C-reactive protein (CRP) concentrations (supplemental vitamin E), cervical cancer (dietary vitamin E), esophageal cancer (dietary vitamin E), cervical intraepithelial neoplasia (CIN, dietary vitamin E), pancreatic cancer (total vitamin E intake), and colorectal cancer (circulating α-tocopherol levels); all of these showed a protective effect consistent with the vitamin E source. In conclusion, our work has indicated that vitamin E is protective for several particular health outcomes. Further prospective studies are required when other factors that may contribute to bias are considered.
Topics: Child; Humans; Vitamin E; alpha-Tocopherol; Antioxidants; Tocopherols; Diet
PubMed: 37571239
DOI: 10.3390/nu15153301 -
Current Opinion in Plant Biology Aug 2023Among the eight forms of vitamin E, only tocopherols are essential compounds that are distributed throughout the entire plant kingdom, with α-tocopherol being the most... (Review)
Review
Among the eight forms of vitamin E, only tocopherols are essential compounds that are distributed throughout the entire plant kingdom, with α-tocopherol being the most predominant form in photosynthetic tissues. At the cellular level, α-tocopherol is of special relevance inside the chloroplast, where it eliminates singlet oxygen and modulates lipid peroxidation. This is of utmost relevance since tocopherols are the only antioxidants that counteract lipid peroxidation. Moreover, at the whole-plant level, α-tocopherol appears to modulate several physiological processes from germination to senescence. The antioxidant role of α-tocopherol at the cellular level can have profound effects at the whole-plant level, including the modulation of physiological processes that are apparently not related to redox processes and could be considered non-antioxidant functions. Here, we discuss whether non-antioxidant functions of α-tocopherol at the whole-plant level are mediated by its antioxidant role in chloroplasts and the regulation of redox processes at the cellular level.
Topics: Antioxidants; alpha-Tocopherol; Vitamin E; Tocopherols; Chloroplasts
PubMed: 37311290
DOI: 10.1016/j.pbi.2023.102400