Enhanced fatty acid oxidation provides glioblastoma cells metabolic plasticity to accommodate to its dynamic nutrient microenvironment.

Despite advances in molecularly characterizing glioblastoma (GBM), metabolic alterations driving its aggressive phenotype are only beginning to be recognized. Integrative cross-platform analysis coupling global metabolomic and gene expression profiling on patient-derived glioma identified fatty acid β-oxidation (FAO) as a metabolic node in GBM. We determined that the biologic consequence of enhanced FAO is directly dependent upon tumor microenvironment.

Age-related murine hippocampal CA1 laminae oxidative stress measured in vivo by QUEnch-assiSTed (QUEST) MRI: impact of isoflurane anesthesia.

Age-related impairments in spatial learning and memory often precede non-familial neurodegenerative disease. Ex vivo studies suggest that physiologic age-related oxidative stress in hippocampus area CA1 may contribute to prodromal spatial disorientation and to morbidity. Yet, conventional blood or cerebrospinal fluid assays appear insufficient for early detection or management of oxidative stress within CA1 sub-regions in vivo.

Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo.

Purpose: To test the hypothesis that imaging biomarkers are useful for evaluating in vivo rod photoreceptor cell responses to a mitochondrial protonophore.

Methods: Intraperitoneal injections of either the mitochondrial uncoupler 2,4 dinitrophenol (DNP) or saline were given to mice with either higher [129S6/eVTac (S6)] or lower [C57BL/6J (B6)] mitochondrial reserve capacities and were studied in dark or light. We measured: (i) the external limiting membrane-retinal pigment epithelium region thickness (ELM-RPE; OCT), which decreases substantially with upregulation of a pH-sensitive water removal co-transporter on the apical portion of the RPE, and (ii) the outer retina R1 (= 1/(spin lattice relaxation time (T1), an MRI parameter proportional to oxygen / free radical content.

Vietnamese Adult-Child and Spousal Caregivers of Older Adults in Houston, Texas: Results from the Vietnamese Aging and Care Survey (VACS).

Vietnamese are the largest Asian ethnic group in Houston, Texas; however, research on this population is scarce. To address this dearth of knowledge, we developed the . The objective of the study was to explore the sociodemographic and health characteristics of Vietnamese adults aged 65 years and older (n = 132) and their family caregivers (n = 64).

Single-dose cardioplegia protects myocardium as well as traditional repetitive dosing: A noninferiority randomized study.

Objective: The present prospective noninferiority randomized trial was designed to demonstrate the safety and efficacy of a single dose of Custodiol histidine-tryptophan-ketoglutarate compared with repetitive cold-blood cardioplegia.

Methods: From October 2012 to May 2014, 110 patients were randomly assigned to 1 of 2 groups: Group 1 (55 patients) received repetitive cold-blood cardioplegia, and group 2 (55 patients) received single-dose Custodiol histidine-tryptophan-ketoglutarate. Isolated aortic valve replacement, isolated mitral valve replacement, and multivalve procedures represented the most frequent operations, with 39 cases (71%) in group 1 and 49 cases (89%) in group 2.

QUEST MRI assessment of fetal brain oxidative stress in utero.

Purpose: To achieve sufficient precision of R1 (=1/T1) maps of the fetal brain in utero to perform QUEnch-assiSTed (QUEST) MRI in which a significant anti-oxidant-induced reduction in R1 indicates oxidative stress.

Methods: C57BL/6 mouse fetuses in utero were gently and non-surgically isolated and secured using a homemade 3D printed clip. Using a commercial receive-only surface coil, brain maps of R1, an index sensitive to excessive and continuous free radical production, were collected using either a conventional Cartesian or a non-Cartesian (periodically rotated overlapping parallel lines with enhanced reconstruction) progressive saturation sequence.

Outer Retinal Oxidative Stress Measured In Vivo Using QUEnch-assiSTed (QUEST) OCT.

Purpose: To test the hypothesis that oxidative stress in the outer retina (OR = distance from external limiting membrane to the retinal pigment epithelium-choroid boundary) can be detected by using antioxidants (AOs) to correct an impaired light-evoked response as measured by optical coherence tomography (OCT).

Methods: C57BL/6J mice were maintained in the dark for ∼20 hours and studied by OCT before and after 1 hour of light exposure. OR thickness in dark or light was measured, and the light-dark difference (i.

Influence of Normal Aging on Brain Autophagy: A Complex Scenario.

Misfolded proteins are pathological findings in some chronic neurodegenerative disorders including Alzheimer's, Parkinson's, and Huntington's diseases. Aging is a major risk factor for these disorders, suggesting that the mechanisms responsible for clearing misfolded proteins from the brain, the ubiquitin-proteasome system and the autophagy-lysosomal pathway, may decline with age. Although autophagic mechanisms have been found to decrease with age in many experimental models, whether they do so in the brain is unclear.

Metabolomic Profiling of Cerebral Palsy Brain Tissue Reveals Novel Central Biomarkers and Biochemical Pathways Associated with the Disease: A Pilot Study.

Cerebral palsy (CP) is one of the most common causes of motor disability in childhood, with complex and heterogeneous etiopathophysiology and clinical presentation. Understanding the metabolic processes associated with the disease may aid in the discovery of preventive measures and therapy. Tissue samples (caudate nucleus) were obtained from post-mortem CP cases ( = 9) and age- and gender-matched control subjects ( = 11).

Mitochondrial Respiration in Outer Retina Contributes to Light-Evoked Increase in Hydration In Vivo.

Purpose: To test the hypothesis that mitochondrial respiration contributes to local changes in hydration involved in phototransduction-driven expansion of outer retina, as measured by structural responses on optical coherence tomography (OCT) and diffusion magnetic resonance imaging (MRI).

Methods: Oxygen consumption rate and mitochondrial reserve capacity of freshly isolated C57BL/6 and 129S6/SvEvTac mouse retina were measured using a Seahorse Extracellular Flux Analyzer. Light-stimulated outer retina layer water content was determined by proton density MRI, structure and thickness by ultrahigh-resolution OCT, and water mobility by diffusion MRI.

Artificial intelligence and amniotic fluid multiomics: prediction of perinatal outcome in asymptomatic women with short cervix.

Objective: To evaluate the application of artificial intelligence (AI), i.e. deep learning and other machine-learning techniques, to amniotic fluid (AF) metabolomics and proteomics, alone and in combination with sonographic, clinical and demographic factors, in the prediction of perinatal outcome in asymptomatic pregnant women with short cervical length (CL).

Evidence That Parietal Lobe Fatty Acids May Be More Profoundly Affected in Moderate Alzheimer's Disease (AD) Pathology Than in Severe AD Pathology.

Brain is a lipid-rich tissue, and fatty acids (FAs) play a crucial role in brain function, including neuronal cell growth and development. This study used GC-MS to survey all detectable FAs in the human parietal cortex (Brodmann area 7). These FAs were accurately quantified in 27 cognitively normal age-matched controls, 16 cases of moderate Alzheimer's disease (AD), 30 severe AD, and 14 dementia with Lewy bodies (DLB).

A Retrospective Evaluation of Time to Obtain an MRI for English- Versus Non-English-Speaking Patients.

Purpose: Americans with limited English proficiency (LEP) face significant barriers to health care that result in health disparities in the LEP population. LEP could delay an MRI, potentially increasing morbidity and mortality in the LEP population. This study compares the time to obtain a neurological MRI in English versus non-English language preference patients.

Tryptophan Metabolism Contributes to Radiation-Induced Immune Checkpoint Reactivation in Glioblastoma.

Immune checkpoint inhibitors designed to revert tumor-induced immunosuppression have emerged as potent anticancer therapies. Tryptophan metabolism represents an immune checkpoint, and targeting this pathway's rate-limiting enzyme IDO1 is actively being investigated clinically. Here, we studied the intermediary metabolism of tryptophan metabolism in glioblastoma and evaluated the activity of the IDO1 inhibitor GDC-0919, both alone and in combination with radiation (RT).

Untargeted metabolomics reveals distinct metabolic reprogramming in endothelial cells co-cultured with CSC and non-CSC prostate cancer cell subpopulations.

Tumour angiogenesis is an important hallmark of cancer and the study of its metabolic adaptations, downstream to any cellular change, can reveal attractive targets for inhibiting cancer growth. In the tumour microenvironment, endothelial cells (ECs) interact with heterogeneous tumour cell types that drive angiogenesis and metastasis. In this study we aim to characterize the metabolic alterations in ECs influenced by the presence of tumour cells with extreme metastatic abilities.

Metabolomic serum profiling after ACL injury in rats: A pilot study implicating inflammation and immune dysregulation in post-traumatic osteoarthritis.

ACL rupture is a major risk factor for post-traumatic osteoarthritis (PTOA) development. Little information exists on acute systemic metabolic indicators of disease development. Thirty-six female Lewis rats were randomized to Control or noninvasive anterior cruciate ligament rupture (ACLR) and to three post-injury time points: 72 h, 4 weeks, 10 weeks (n = 6).

Specific serum antibody binding to phosphorylated and non-phosphorylated tau in non-cognitively impaired, mildly cognitively impaired, and Alzheimer's disease subjects: an exploratory study.

Background: Tau vaccination and administration of anti-tau antibodies can prevent pathology and cognitive impairment in transgenic mouse models of tauopathy, suggesting that therapies which increase anti-tau antibodies might slow the development and/or progression of Alzheimer's disease (AD). The extent to which individuals with no cognitive impairment (NCI) possess serum anti-tau antibodies, and whether their concentrations of these antibodies differ from anti-tau antibody levels in persons with mild cognitive impairment (MCI) or AD, are unclear. Previous studies measuring these antibodies did not account for antibody polyvalent binding, which can be extensive, nor that antibody binding to phosphorylated tau peptides could be due to binding to non-phosphorylated epitopes on those peptides.

Metabolomic Profiling of Bile Acids in Clinical and Experimental Samples of Alzheimer's Disease.

Certain endogenous bile acids have been proposed as potential therapies for ameliorating Alzheimer's disease (AD) but their role, if any, in the pathophysiology of this disease is not currently known. Given recent evidence of bile acids having protective and anti-inflammatory effects on the brain, it is important to establish how AD affects levels of endogenous bile acids. Using LC-MS/MS, this study profiled 22 bile acids in brain extracts and blood plasma from AD patients (n = 10) and age-matched control subjects (n = 10).

Diagnostic Biomarkers of Alzheimer's Disease as Identified in Saliva using 1H NMR-Based Metabolomics.

Using 1H NMR metabolomics, we biochemically profiled saliva samples collected from healthy-controls (n = 12), mild cognitive impairment (MCI) sufferers (n = 8), and Alzheimer's disease (AD) patients (n = 9). We accurately identified significant concentration changes in 22 metabolites in the saliva of MCI and AD patients compared to controls. This pilot study demonstrates the potential for using metabolomics and saliva for the early diagnosis of AD.

Impact of Anticoagulation in Elderly Patients With Pulmonary Embolism That Undergo IVC Filter Placement: A Retrospective Cohort Study.

Background: Anticoagulation is the primary treatment for pulmonary embolism (PE). Inferior vena cava (IVC) filters are an adjunctive intervention to prevent recurrent pulmonary embolism. Long-term outcomes in elderly patients with contraindications to anticoagulation after IVC filter placement for prevention of recurrent pulmonary embolism have yet to be assessed.

β-methylamino-L-alanine (BMAA) is not found in the brains of patients with confirmed Alzheimer's disease.

Controversy surrounds the proposed hypothesis that exposure to β-methylamino-L-alanine (BMAA) could play a role in various neurodegenerative conditions including Alzheimer's disease (AD). Here we present the results of the most comprehensive scientific study on BMAA detection ever undertaken on brain samples from patients pathologically confirmed to have suffered from AD, and those from healthy volunteers. Following the full validation of a highly accurate and sensitive mass spectrometric method, no trace of BMAA was detected in the diseased brain or in the control specimens.

Treatment of lean and diet-induced obesity (DIO) mice with a novel stable obestatin analogue alters plasma metabolite levels as detected by untargeted LC-MS metabolomics.

Introduction: Obestatin is a controversial gastrointestinal peptide purported to have metabolic actions.

Objectives: This study investigated whether treatment with a stable obestatin analogue (PEG-OB(Cys, Cys)) changed plasma metabolite levels firstly in lean and subsequently in diet-induced obesity (DIO) C57BL6/J mice.

Methods: Untargeted LC-HRMS metabolomics experiments were carried out in ESI + mode with plasma extracts from both groups of animals.

Metabolic signatures of Huntington's disease (HD): (1)H NMR analysis of the polar metabolome in post-mortem human brain.

Huntington's disease (HD) is an autosomal neurodegenerative disorder affecting approximately 5-10 persons per 100,000 worldwide. The pathophysiology of HD is not fully understood but the age of onset is known to be highly dependent on the number of CAG triplet repeats in the huntingtin gene. Using (1)H NMR spectroscopy this study biochemically profiled 39 brain metabolites in post-mortem striatum (n=14) and frontal lobe (n=14) from HD sufferers and controls (n=28).

Wide-ranging alterations in the brain fatty acid complement of subjects with late Alzheimer's disease as detected by GC-MS.

Disturbed lipid metabolism is a well-established feature of human Alzheimer's disease (AD). The present study used gas chromatography-mass spectrometry (GC-MS) analysis of fatty acid methyl esters (FAMES) to profile all detectable fatty acid (FA) species present in post-mortem neocortical tissue (Brodmann 7 region). Quantitative targeted analysis was undertaken from 29 subjects (n=15 age-matched controls; n=14 late-stage AD).

Novel Metabolite Biomarkers of Huntington's Disease As Detected by High-Resolution Mass Spectrometry.

Huntington's disease (HD) is a fatal autosomal-dominant neurodegenerative disorder that affects approximately 3-10 people per 100 000 in the Western world. The median age of onset is 40 years, with death typically following 15-20 years later. In this study, we biochemically profiled post-mortem frontal lobe and striatum from HD sufferers (n = 14) and compared their profiles with controls (n = 14).