Inflammation subsequent to mild iron excess differentially alters regional brain iron metabolism, oxidation and neuroinflammation status in mice.

Iron dyshomeostasis and neuroinflammation, characteristic features of the aged brain, and exacerbated in neurodegenerative disease, may induce oxidative stress-mediated neurodegeneration. In this study, the effects of potential priming with mild systemic iron injections on subsequent lipopolysaccharide (LPS)-induced inflammation in adult C57Bl/6J mice were examined. After cognitive testing, regional brain tissues were dissected for iron (metal) measurements by total reflection X-ray fluorescence and synchrotron radiation X-Ray fluorescence-based elemental mapping; and iron regulatory, ferroptosis-related, and glia-specific protein analysis, and lipid peroxidation by western blotting.

Quantitative MRI susceptibility mapping reveals cortical signatures of changes in iron, calcium and zinc in malformations of cortical development in children with drug-resistant epilepsy.

Objective: Malformations of cortical development (MCD), including focal cortical dysplasia (FCD), are the most common cause of drug-resistant focal epilepsy in children. Histopathological lesion characterisation demonstrates abnormal cell types and lamination, alterations in myelin (typically co-localised with iron), and sometimes calcification. Quantitative susceptibility mapping (QSM) is an emerging MRI technique that measures tissue magnetic susceptibility (χ) reflecting it's mineral composition.

Iron dyshomeostasis, lipid peroxidation and perturbed expression of cystine/glutamate antiporter in Alzheimer's disease: Evidence of ferroptosis.

Iron dyshomeostasis is implicated in Alzheimer's disease (AD) alongside β-amyloid and tau pathologies. Despite the recent discovery of ferroptosis, an iron-dependent form cell death, hitherto, in vivo evidence of ferroptosis in AD is lacking. The present study uniquely adopts an integrated multi-disciplinary approach, combining protein (Western blot) and elemental analysis (total reflection X-ray fluorescence) with metabolomics (H nuclear magnetic resonance spectroscopy) to identify iron dyshomeostasis and ferroptosis, and possible novel interactions with metabolic dysfunction in age-matched male cognitively normal (CN) and AD post-mortem brain tissue (n = 7/group).

Monocarboxylate transporter 1 blockade with AZD3965 inhibits lipid biosynthesis and increases tumour immune cell infiltration.

Background: Monocarboxylate transporter 1 (MCT1) is a regulator of cell metabolism and a therapeutic target for cancer treatment. Understanding the changes in tumour function accompanying MCT1 inhibition will better characterise the anti-tumour effects of MCT1 inhibitors, potentially enabling the identification of pharmacodynamic biomarkers for the clinical development of these agents.

Methods: We assessed the impact of the MCT1 inhibitor AZD3965 on tumour metabolism and immune cell infiltration as key determinants of tumour biological function in the MCT1-dependent Raji B cell lymphoma model.

Determining bacterial and host contributions to the human salivary metabolome.

Background: Salivary metabolomics is rapidly advancing.

Aim And Methods: To determine the extent to which salivary metabolites reflects host or microbial metabolic activity whole-mouth saliva (WMS), parotid saliva (PS) and plasma collected contemporaneously from healthy volunteers were analysed by H-NMR spectroscopy. Spectra underwent principal component analysis and k-means cluster analysis and metabolite quantification.

Publisher Correction: Pattern of Altered Plasma Elemental Phosphorus, Calcium, Zinc, and Iron in Alzheimer's Disease.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Pattern of Altered Plasma Elemental Phosphorus, Calcium, Zinc, and Iron in Alzheimer's Disease.

Metal/mineral dyshomeostasis has been implicated in the development of Alzheimer's disease (AD). The aim of the study was to investigate the difference in absolute and percentage levels of plasma phosphorus, calcium, iron, zinc, copper, selenium in cognitively normal (CN) and AD subjects. Total reflection X-ray fluorescence (TXRF) spectroscopy was used to detect plasma metals/minerals in CN and AD subjects (n = 44 per group).

Developing and Standardizing a Protocol for Quantitative Proton Nuclear Magnetic Resonance (H NMR) Spectroscopy of Saliva.

Metabolic profiling by H NMR spectroscopy is an underutilized technology in salivary research, although preliminary studies have identified promising results in multiple fields (diagnostics, nutrition, sports physiology). Translation of preliminary findings into validated, clinically approved knowledge is hindered by variability in protocol for the collection, storage, preparation, and analysis of saliva. This study aims to evaluate the effects of differing sample pretreatments on the H NMR metabolic profile of saliva.

MCT1 Inhibitor AZD3965 Increases Mitochondrial Metabolism, Facilitating Combination Therapy and Noninvasive Magnetic Resonance Spectroscopy.

Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination strategies or identify pharmacodynamic biomarkers to support the clinical development of MCT inhibitors now in clinical trials. In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism and Exposing human lymphoma and colon carcinoma cells to AZD3965 increased MCT4-dependent accumulation of intracellular lactate, inhibiting monocarboxylate influx and efflux.

The BRAF Inhibitor Vemurafenib Activates Mitochondrial Metabolism and Inhibits Hyperpolarized Pyruvate-Lactate Exchange in BRAF-Mutant Human Melanoma Cells.

Understanding the impact of BRAF signaling inhibition in human melanoma on key disease mechanisms is important for developing biomarkers of therapeutic response and combination strategies to improve long-term disease control. This work investigates the downstream metabolic consequences of BRAF inhibition with vemurafenib, the molecular and biochemical processes that underpin them, their significance for antineoplastic activity, and potential as noninvasive imaging response biomarkers. H NMR spectroscopy showed that vemurafenib decreases the glycolytic activity of BRAF-mutant (WM266.

Dissociation between iron accumulation and ferritin upregulation in the aged substantia nigra: attenuation by dietary restriction.

Despite regulation, brain iron increases with aging and may enhance aging processes including neuroinflammation. Increases in magnetic resonance imaging transverse relaxation rates, R2 and R2*, in the brain have been observed during aging. We show R2 and R2* correlate well with iron content via direct correlation to semi-quantitative synchrotron-based X-ray fluorescence iron mapping, with age-associated R2 and R2* increases reflecting iron accumulation.

Development of a temperature-controlled phantom for magnetic resonance quality assurance of diffusion, dynamic, and relaxometry measurements.

Purpose: Diffusion-weighted (DW) and dynamic contrast-enhanced magnetic resonance imaging (MRI) are increasingly applied for the assessment of functional tissue biomarkers for diagnosis, lesion characterization, or for monitoring of treatment response. However, these techniques are vulnerable to the influence of various factors, so there is a necessity for a standardized MR quality assurance procedure utilizing a phantom to facilitate the reliable estimation of repeatability of these quantitative biomarkers arising from technical factors (e.g.

Determining the chemical exchange saturation transfer (CEST) behavior of citrate and spermine under in vivo conditions.

Purpose: To estimate the exchange rates of labile (1) H in citrate and spermine, metabolites present in prostatic secretions, to predict the size of the citrate and spermine CEST effects in vivo.

Methods: CEST z-spectra were acquired at high-field [11.7 Tesla (T)] from citrate and spermine solutions at physiological pH (6.

Model free approach to kinetic analysis of real-time hyperpolarized 13C magnetic resonance spectroscopy data.

Real-time detection of the rates of metabolic flux, or exchange rates of endogenous enzymatic reactions, is now feasible in biological systems using Dynamic Nuclear Polarization Magnetic Resonance. Derivation of reaction rate kinetics from this technique typically requires multi-compartmental modeling of dynamic data, and results are therefore model-dependent and prone to misinterpretation. We present a model-free formulism based on the ratio of total areas under the curve (AUC) of the injected and product metabolite, for example pyruvate and lactate.

In vivo imaging of glucose uptake and metabolism in tumors.

Tumors have a greater reliance on anaerobic glycolysis for energy production than normal tissues. We developed a noninvasive method for imaging glucose uptake in vivo that is based on magnetic resonance imaging and allows the uptake of unlabeled glucose to be measured through the chemical exchange of protons between hydroxyl groups and water. This method differs from existing molecular imaging methods because it permits detection of the delivery and uptake of a metabolically active compound in physiological quantities.

¹H NMR and hyperpolarized ¹³C NMR assays of pyruvate-lactate: a comparative study.

Pyruvate-lactate exchange is mediated by the enzyme lactate dehydrogenase (LDH) and is central to the altered energy metabolism in cancer cells. The measurement of exchange kinetics using hyperpolarized (13) C NMR has provided a biomarker of response to novel therapeutics. However, the observable signal is restricted to the exchanging hyperpolarized (13) C pools and the endogenous pools of (12) C-labelled metabolites are invisible in these measurements.

Targeting of the pedunculopontine nucleus by an MRI-guided approach: a cadaver study.

Laboratory evidence suggests that the pedunculopontine nucleus (PPN) plays a central role in the initiation and maintenance of gait. Translational research has led to reports on deep brain stimulation (DBS) of the rostral brainstem in parkinsonian patients. However, initial clinical results appear to be rather variable.

Efficient and rapid labeling of transplanted cell populations with superparamagnetic iron oxide nanoparticles using cell surface chemical biotinylation for in vivo monitoring by MRI.

Determination of the dynamics of specific cell populations in vivo is essential for the development of cell-based therapies. For cell tracking by magnetic resonance imaging (MRI), cells need to internalize, or be surface labeled with a MRI contrast agent, such as superparamagnetic iron oxide nanoparticles (SPIOs): SPIOs give rise to signal loss by gradient-echo and T(2)-weighted MRI techniques. In this study, cancer cells were chemically tagged with biotin and then magnetically labeled with anti-biotin SPIOs.

High field (9.4 Tesla) magnetic resonance imaging of cortical grey matter lesions in multiple sclerosis.

Multiple sclerosis is an inflammatory, degenerative disease of the central nervous system. The most obvious pathological change in multiple sclerosis is multifocal demyelination of the white matter, but grey matter demyelination may be of equal or even greater importance for its clinical manifestations. In order to assess the pathogenetic role of lesions in the grey and white matter, and to explore the association between demyelinated and non-lesional brain tissue, tools are needed to depict each of these tissue components accurately in vivo.

Quantitative magnetic resonance of postmortem multiple sclerosis brain before and after fixation.

Unfixed and fixed postmortem multiple sclerosis (MS) brain is being used to probe pathology underlying quantitative MR (qMR) changes. Effects of fixation on qMR indices in MS brain are unknown. In 15 postmortem MS brain slices T(1), T(2), MT ratio (MTR), macromolecular proton fraction (f(B)), fractional anisotropy (FA), and mean, axial, and radial diffusivity (MD, D(ax), and D(rad)) were assessed in white matter (WM) lesions (WML) and normal appearing WM (NAWM) before and after fixation in formalin.

Tissue-specific differences in 2-fluoro-2-deoxyglucose metabolism beyond FDG-6-P: a 19F NMR spectroscopy study in the rat.

2-Fluoro-[(18)F]-2-deoxy-glucose (FDG) is a positron-emitting analogue of glucose used clinically in positron emission tomography (PET) to assess glucose utilization in diseased and healthy tissue. Originally developed to measure local cerebral glucose utilization rates, it has now found applications in tumour diagnosis and in the study of myocardial glucose uptake. Once taken up into the cell, FDG is phosphorylated to FDG-6-phosphate (FDG-6-P) by hexokinase and was originally believed to be trapped as a terminal metabolite.