0
selected
-
1.
Brain on food: The neuroepigenetics of nutrition.
Vaziri, A, Dus, M
Neurochemistry international. 2021;:105099
-
-
Free full text
-
Abstract
Humans have known for millennia that nutrition has a profound influence on health and disease, but it is only recently that we have begun mapping the mechanisms via which the dietary environment impacts brain physiology and behavior. Here we review recent evidence on the effects of energy-dense and methionine diets on neural epigenetic marks, gene expression, and behavior in invertebrate and vertebrate model organisms. We also discuss limitations, open questions, and future directions in the emerging field of the neuroepigenetics of nutrition.
-
2.
Oral Methioninase for Covid-19 Methionine-restriction Therapy.
Hoffman, RM, Han, Q
In vivo (Athens, Greece). 2020;(3 Suppl):1593-1596
-
-
Free full text
-
Abstract
The Covid-19 pandemic is a world-wide crisis without an effective therapy. While most approaches to therapy are using repurposed drugs that were developed for other diseases, it is thought that targeting the biology of the SARS-CoV-2 virus, which causes Covid-19, can result in an effective therapeutic treatment. The coronavirus RNA cap structure is methylated by two viral methyltransferases that transfer methyl groups from S-adenosylmethionine (SAM). The proper methylation of the virus depends on the level of methionine in the host to form SAM. Herein, we propose to restrict methionine availability by treating the patient with oral recombinant methioninase, aiming to treat Covid-19. By restricting methionine we not only interdict viral replication, which depends on the viral RNA cap methyaltion, but also inhibit the proliferation of the infected cells, which have an increased requirement for methionine. Most importantly, the virally-induced T-cell- and macrophage-mediated cytokine storm, which seems to be a significant cause for Covid-19 deaths, can also be inhibited by restricting methionine, since T-cell and macrophrage activation greatly increases the methionine requirement for these cells. The evidence reviewed here suggests that oral recombinant methioninase could be a promising treatment for coronavirus patients.
-
3.
Vitamin B Supplementation and Nutritional Intake of Methyl Donors in Patients with Chronic Kidney Disease: A Critical Review of the Impact on Epigenetic Machinery.
Cappuccilli, M, Bergamini, C, Giacomelli, FA, Cianciolo, G, Donati, G, Conte, D, Natali, T, La Manna, G, Capelli, I
Nutrients. 2020;(5)
Abstract
Cardiovascular morbidity and mortality are several-fold higher in patients with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) than in the general population. Hyperhomocysteinemia has undoubtedly a central role in such a prominent cardiovascular burden. The levels of homocysteine are regulated by methyl donors (folate, methionine, choline, betaine), and cofactors (vitamin B6, vitamin B12,). Uremia-induced hyperhomocysteinemia has as its main targets DNA methyltransferases, and this leads to an altered epigenetic control of genes regulated through methylation. In renal patients, the epigenetic landscape is strictly correlated with the uremic phenotype and dependent on dietary intake of micronutrients, inflammation, gut microbiome, inflammatory status, oxidative stress, and lifestyle habits. All these factors are key contributors in methylome maintenance and in the modulation of gene transcription through DNA hypo- or hypermethylation in CKD. This is an overview of the epigenetic changes related to DNA methylation in patients with advanced CKD and ESRD. We explored the currently available data on the molecular dysregulations resulting from altered gene expression in uremia. Special attention was paid to the efficacy of B-vitamins supplementation and dietary intake of methyl donors on homocysteine lowering and cardiovascular protection.
-
4.
Autism spectrum disorder (ASD) - biomarkers of oxidative stress and methylation and transsulfuration cycle.
Waligóra, A, Waligóra, S, Kozarska, M, Damasiewicz-Bodzek, A, Gorczyca, P, Tyrpień-Golder, K
Psychiatria polska. 2019;(4):771-788
Abstract
Autism spectrum disorder (ASD) affects people from all regions of the globe, regardless of nationality, living standards or social group. Currently, it is assumed that ASD pathogenesis is multifactorial because there is no one specific cause of the disorder. According to literature, ASD may result from genetic defects, metabolic disorders or exposure to environmental factors. There is a number of hypotheses that attempt to explain the intensity of emotional and behavioral symptoms or the increased sensory threshold that is characteristic of ASD. It is suggested that neurological changes may be due to oxidative stress occurring in early brain tissue development and reduced antioxidative barrier. Due to the abnormalities in the synthesis of neurotransmitters, often occurring in ASD, autism is investigated for disorders of vital biochemical processes of methylation and transsulfuration. Finding a biomarker for a disturbed oxidative-reduction equilibrium, methylation pathway pathology, or other reason could be an important diagnostic tool and the base for individual treatment for patients with varying degrees of severity. This work provides a review of the potential biological indicators for ASD taking into account the occurrence of oxidative stress and the methylation and transsulfuration cycles.
-
5.
The use of amino acid PET and conventional MRI for monitoring of brain tumor therapy.
Galldiks, N, Law, I, Pope, WB, Arbizu, J, Langen, KJ
NeuroImage. Clinical. 2017;:386-394
Abstract
Routine diagnostics and treatment monitoring of brain tumors is usually based on contrast-enhanced MRI. However, the capacity of conventional MRI to differentiate tumor tissue from posttherapeutic effects following neurosurgical resection, chemoradiation, alkylating chemotherapy, radiosurgery, and/or immunotherapy may be limited. Metabolic imaging using PET can provide relevant additional information on tumor metabolism, which allows for more accurate diagnostics especially in clinically equivocal situations. This review article focuses predominantly on the amino acid PET tracers 11C-methyl-l-methionine (MET), O-(2-[18F]fluoroethyl)-l-tyrosine (FET) and 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (FDOPA) and summarizes investigations regarding monitoring of brain tumor therapy.
-
6.
Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis.
Ingenbleek, Y
Nutrients. 2017;(9)
Abstract
Protein-depleted states generate allosteric inhibition of liver cystathionine β-synthase (CBS), which governs the first enzymatic step of the transsulfuration cascade, resulting in upstream accretion of homocysteine (Hcy) in body fluids. A similar Hcy increase may arise from normal hepatocytes undergoing experimentally-induced impairment of betaine-homocysteine methyltransferase (BHTM) activity or from components of lean body mass (LBM) submitted to any inflammatory disorder. LBM comprises a composite agglomeration of extrarenal tissues characterized by naturally occurring BHTM inactivity. As a result of cellular injury, LBM releases high concentrations of Hcy into the extracellular space, contrasting with the disruption of normal remethylation pathways. Hyperhomocysteinemia acts as a biomarker, reflecting the severity of insult and operating as an alarm signal. Elevated Hcy levels constitute a precursor pool recognized by a CBS coding region that reacts to meet increased methionine requirements in LBM tissues, using its enhanced production in hepatocytes. Preservation of methionine homeostasis benefits from its high metabolic priority and survival value.
-
7.
[Research advances in the association between maternal intake of methyl donor nutrients during pregnancy and DNA methylation in offspring].
Wu, MM, Yang, F
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics. 2017;(5):601-606
Abstract
Maternal nutrition during pregnancy plays a vital role in the health of the offspring. Methyl donor nutrients, including folate, vitamin B12, choline, betaine, and methionine, directly affect DNA methylation and are closely associated with the health of the offspring. As an important part of epigenetics, DNA methylation plays an important role in the maintenance of normal cellular function, gene expression regulation, and embryonic development. Recent studies have shown that maternal nutrition may have a long-lasting effect on the health of the offspring via the changes in genomic DNA and/or methylation level in the promoter region in specific genes. Therefore, this review article focuses on the effect of maternal intake of methyl donor nutrients during pregnancy on DNA methylation, in order to explore the effect of the changed methylation status on the health of the offspring at the molecular level.
-
8.
A meta-analysis on the diagnostic performance of (18)F-FDG and (11)C-methionine PET for differentiating brain tumors.
Zhao, C, Zhang, Y, Wang, J
AJNR. American journal of neuroradiology. 2014;(6):1058-65
Abstract
(18)F-FDG-PET has been widely used in patients with brain tumors. However, the reported sensitivity and specificity of (18)F-FDG-PET for brain tumor differentiation varied greatly. We performed this meta-analysis to systematically assess the diagnostic performance of (18)F-FDG-PET in differentiating brain tumors. The diagnostic performance of (11)C-methionine PET was assessed for comparison. Relevant studies were searched in PubMed/MEDLINE, Scopus, and China National Knowledge Infrastructure (until February 2013). The methodologic quality of eligible studies was evaluated, and a meta-analysis was performed to obtain the combined diagnostic performance of (18)F-FDG and (11)C-methionine PET with a bivariate model. Thirty eligible studies, including 5 studies with both (18)F-FDG and (11)C-methionine PET data were enrolled. Pooled sensitivity, pooled specificity, and area under the receiver operating characteristic curve of (18)F-FDG-PET (n = 24) for differentiating brain tumors were 0.71 (95% CI, 0.63-0.78), 0.77 (95% CI, 0.67-0.85), and 0.80. Heterogeneity was found among (18)F-FDG studies. Subsequent subgroup analysis revealed that the disease status was a statistically significant source of the heterogeneity and that the sensitivity in the patients with recurrent brain tumor was markedly higher than those with suspected primary brain tumors. Pooled sensitivity, pooled specificity, and area under the receiver operating characteristic of (11)C-methionine PET (n = 11) were 0.91 (95% CI, 0.85-0.94), 0.86 (95% CI, 0.78-0.92), and 0.94. No significant statistical heterogeneity was found among (11)C-methionine studies. This meta-analysis suggested that (18)F-FDG-PET has limited diagnostic performance in brain tumor differentiation, though its performance may vary according to the status of brain tumor, whereas (11)C-methionine PET has excellent diagnostic accuracy in brain tumor differentiation.
-
9.
Interaction between stress and the BDNF Val66Met polymorphism in depression: a systematic review and meta-analysis.
Hosang, GM, Shiles, C, Tansey, KE, McGuffin, P, Uher, R
BMC medicine. 2014;:7
Abstract
BACKGROUND Major depression is a disabling psychiatric illness with complex origins. Life stress (childhood adversity and recent stressful events) is a robust risk factor for depression. The relationship between life stress and Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has received much attention. The aim of the present work was to review and conduct a meta-analysis on the results from published studies examining this interaction. METHODS A literature search was conducted using PsychINFO and PubMed databases until 22 November 2013. A total of 22 studies with a pooled total of 14,233 participants met the inclusion criteria, the results of which were combined and a meta-analysis performed using the Liptak-Stouffer z-score method. RESULTS The results suggest that the Met allele of BDNF Val66Met significantly moderates the relationship between life stress and depression (P = 0.03). When the studies were stratified by type of environmental stressor, the evidence was stronger for an interaction with stressful life events (P = 0.01) and weaker for interaction of BDNF Val66Met with childhood adversity (P = 0.051). CONCLUSIONS The interaction between BDNF and life stress in depression is stronger for stressful life events rather than childhood adversity. Methodological limitations of existing studies include poor measurement of life stress.
-
10.
Bacterial methionine biosynthesis.
Ferla, MP, Patrick, WM
Microbiology (Reading, England). 2014;(Pt 8):1571-1584
Abstract
Methionine is essential in all organisms, as it is both a proteinogenic amino acid and a component of the cofactor, S-adenosyl methionine. The metabolic pathway for its biosynthesis has been extensively characterized in Escherichia coli; however, it is becoming apparent that most bacterial species do not use the E. coli pathway. Instead, studies on other organisms and genome sequencing data are uncovering significant diversity in the enzymes and metabolic intermediates that are used for methionine biosynthesis. This review summarizes the different biochemical strategies that are employed in the three key steps for methionine biosynthesis from homoserine (i.e. acylation, sulfurylation and methylation). A survey is presented of the presence and absence of the various biosynthetic enzymes in 1593 representative bacterial species, shedding light on the non-canonical nature of the E. coli pathway. This review also highlights ways in which knowledge of methionine biosynthesis can be utilized for biotechnological applications. Finally, gaps in the current understanding of bacterial methionine biosynthesis are noted. For example, the paper discusses the presence of one gene (metC) in a large number of species that appear to lack the gene encoding the enzyme for the preceding step in the pathway (metB), as it is understood in E. coli. Therefore, this review aims to move the focus away from E. coli, to better reflect the true diversity of bacterial pathways for methionine biosynthesis.