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A Pex7 Deficient Mouse Series Correlates Biochemical and Neurobehavioral Markers to Genotype Severity-Implications for the Disease Spectrum of Rhizomelic Chondrodysplasia Punctata Type 1.

Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a peroxisome biogenesis disorder caused by defects in PEX7 leading to impairment in plasmalogen (Pls) biosynthesis and phytanic acid (PA) oxidation. Pls deficiency is the main pathogenic factor that determines the severity of RCDP. Severe (classic) RCDP patients have negligible Pls levels, congenital cataracts, skeletal dysplasia, growth and neurodevelopmental deficits, and cerebral hypomyelination and cerebellar atrophy on brain MRI. Individuals with milder or nonclassic RCDP have higher Pls levels, better growth and cognitive outcomes. T

The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium.

BACKGROUND: Excess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecula … spholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10-8). In contrast, 4 amino acids, including glutamate (OR for 1 SD …

Role of lipids in pathophysiology, diagnosis and therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an aggressive and widespread cancer. Patients with liver cirrhosis of different aetiologies are at a risk to develop HCC. It is important to know that in approximately 20% of cases primary liver tumors arise in a non-cirrhotic liver. Lipid metabolism is variable in patients with chronic liver diseases, and lipid metabolites involved therein do play a role in the development of HCC. Of note, lipid composition of carcinogenic tissues differs from non-affected liver tissues. High cholesterol and low ceramide levels in the tumors protect the cells from oxidative s

Genotypic and phenotypic diversity of PGPR fluorescent pseudomonads isolated from the rhizosphere of sugarcane (Saccharum officinarum L.).

The genetic diversity of plant growth-promoting rhizobacterial (PGPR) fluorescent pseudomonads associated with the sugarcane (Saccharum officinarum L.) rhizosphere was analyzed. Selected isolates were screened for plant growthpromoting properties including production of indole acetic acid, phosphate solubilization, denitrification ability, and production of antifungal metabolites. Furthermore, 16S rDNA sequence analysis was performed to identify and differentiate these isolates. Based on 16S rDNA sequence similarity, the isolates were designated as Pseudomonas plecoglossicida, P. fluorescens,

Sudden infant death syndrome and abnormal metabolism of thiamin.

Although it has been generally accepted that moving the infant from the prone to the supine position has solved the problem of sudden infant death syndrome (SIDS), it has been hypothesized that this is an insufficient explanation and that a mixture of genetic risk, some form of stressful incident and marginal brain metabolism is proportionately required. It is suggested that each of these three variables, with dominance in one or more of them, act together in the common etiology. Much has been written about the association of thiamin and magnesium but the finding of extremely high concentratio

Metabolomic biomarkers of rest-activity rhythms in older women: results from the Women's Health Initiative study.

STUDY OBJECTIVES: Prior research has suggested that disrupted and weakened rest-activity rhythms measured by accelerometry may be associated … range of biochemical classes and metabolic pathways, including sulfur amino acids, fibrinopeptides, plasmalogens, amino sugar metabolites, and nucleotides. The PEX5 gene network was identified by the Ingenuity Pathway Analysis as the most significantly enriched genetic pathway in relation to rest-activity rhythms. CONCLUSIONS: We found numerous metabolites an …

Lipid composition of the nervous system in Refsum's disease.

The compositions of the major lipids and their constituent fatty acids and fatty aldehydes from cerebral gray matter, white matter, and myelin, spinal cord myelin, and sciatic nerve were determined in a 57 yr old woman who died of Refsum's disease. There were deficiencies of ethanolamine glycerophosphatides (EGP) in gray matter and frontal lobe myelin, and a lipid with the chromatographic properties of lyso-EGP accumulated in all tissues. The proportions of the remaining lipids were nearly normal in the central nervous system tissues. In the sciatic nerve the proportions of sphingolipids were

Association of Plasma Metabolomic Biomarkers With Persistent Tinnitus: A Population-Based Case-Control Study.

IMPORTANCE: Persistent tinnitus is common, disabling, and difficult to treat. OBJECTIVE: To evaluate the association between circulating me … s (NES, 2.48), and diglycerides (NES, 1.65) were positively associated, whereas phosphatidylcholine plasmalogens (NES, -1.91), lysophosphatidylcholines (NES, -2.23), and cholesteryl esters (NES,-2.31) were inversely associated with persistent tinnitus. CONCLUSIONS AND RELEVANCE: This population-based case-control study of metabolomic profiles and tinnitus ide …

Myeloperoxidase instigates proinflammatory responses in a cecal ligation and puncture rat model of sepsis.

Myeloperoxidase (MPO)-derived hypochlorous (HOCl) reacts with membrane plasmalogens to yield α-chlorofatty aldehydes such as 2-chlorofatty aldehyde (2-ClFALD) and its metabolite 2-chlorofatty acid (2-ClFA). Recent studies showed that 2-ClFALD and 2-ClFA serve as mediators of the inflammatory responses to sepsis by as yet unknown mechanisms. Since no scavenger for chlorinated lipids is available and on the basis of the well-established role of the MPO/HOCl/chlorinated lipid axis in inflammatory responses, we hypothesized that treatment with MPO inhibitors (N-acetyl lysyltyrosylcysteine amide or…

Metabolomic biomarkers of rest-activity rhythms in older men: results from the Osteoporotic Fractures in Men (MrOS) study.

STUDY OBJECTIVES: Rest-activity rhythm characteristics have been linked to a wide range of health conditions; however, the molecular mechanisms underlying these associations are not well understood. This study is the first of two studies aiming to use an untargeted approach to identify metabolomic markers associated with rest-activity rhythm characteristics and focuses on older men. METHODS: The study included 950 participants from the Osteoporotic Fractures in Men study. Multiple parametric and non-parametric variables of rest-activity rhythms were derived from actigraphy data. A total of 84

Serum metabolite signature of the mediterranean diet adherence and cognitive function: Evidence from two cohorts.

BACKGROUND AND AIMS: The Mediterranean diet (MD) has been consistently associated with favorable cognitive outcomes. However, reliance on self-reported dietary assessment limits accurate characterization of diet-health associations. Circulating metabolites may capture the endogenous metabolic imprint of habitual dietary patterns and provide complementary biological information beyond questionnaire-based measures. We aimed to identify a serum metabolite signature associated with MD adherence and to examine its cross-cohort reproducibility and associations with cognitive performance and trajecto

Ethanolaminephosphate cytidyltransferase is essential for survival, lipid homeostasis and stress tolerance in Leishmania major.

UNLABELLED: Glycerophospholipids including phosphatidylethanolamine (PE) and phosphatidylcholine (PC) are vital components of biological membranes. Trypanosomatid parasites of the genus Leishmania can acquire PE and PC via de novo synthesis and the uptake/remodeling of host lipids. In this study, we investigated the ethanolaminephosphate cytidyltransferase (EPCT) in Leishmania major , which is the causative agent for cutaneous leishmaniasis. EPCT is a key enzyme in the ethanolamine branch of the Kennedy pathway which is responsible for the de novo synthesis of PE. Our results demonstrate that

Lipidomic profiling reveals early-stage metabolic dysfunction in overweight or obese humans.

BACKGROUND: Advances in mass spectrometry and lipidomics techniques are providing new insights into the role of lipid metabolism in obesity-related diseases. However, human lipidomic studies have been inconsistent, owing to the use of indirect proxy measures of metabolic outcomes and relatively limited coverage of the lipidome. Here, we employed comprehensive lipid profiling and gold-standard metabolic measures to test the hypothesis that distinct lipid signatures in obesity may signify early stages of pathogenesis toward type 2 diabetes. METHODS: Using high-performance liquid chromatography-

Metabolomic profiles of chronic distress are associated with cardiovascular disease risk and inflammation-related risk factors.

BACKGROUND: Chronic psychological distress is associated with increased risk of cardiovascular disease (CVD) and investigators have posited inflammatory factors may be centrally involved in these relationships. However, mechanistic evidence and molecular underpinnings of these processes remain unclear, and data are particularly sparse among women. This study examined if a metabolite profile linked with distress was associated with increased CVD risk and inflammation-related risk factors. METHODS: A plasma metabolite-based distress score (MDS) of twenty chronic psychological distress-related m

Oral Disease and Atherosclerosis May Be Associated with Overlapping Metabolic Pathways.

OBJECTIVES: Dental caries and periodontitis are among the most prevalent chronic diseases worldwide and have been associated with atherosclerotic cardiovascular diseases (ASCVD). This study aimed to determine (1) the independent associations between subclinical ASCVD markers (carotid intima media thickness [CIMT] and coronary artery calcification [CAC]) and quantitative indices of oral disease including the decayed, missing, and filled teeth (DMFT) index, gingivitis parameters, periodontal status, and number of teeth lost and (2) the extent to which metabolites altered in individuals with oral

Early life infection and proinflammatory, atherogenic metabolomic and lipidomic profiles in infancy: a population-based cohort study.

BACKGROUND: The risk of adult onset cardiovascular and metabolic (cardiometabolic) disease accrues from early life. Infection is ubiquitous … s (elevated phosphatidylethanolamines and lower trihexosylceramides, dehydrocholesteryl esters, and plasmalogens). Similar, more marked, profiles were observed with higher GlycA, but not hsCRP. GlycA mediated a substantial proportion of the relationship between infection and metabolome/lipidome, with hsCRP generally mediating a lower proportion. Analogous rela …

Микроглиа регулирует расчистку миелин и метаболизм холестерина после демиелинации с помощью интерферона регулирующего коэффициента 5.

Регулирующий фактор интерферона 5 (IRF5) — это фактор транскрипции, который играет определенную роль в организации врожденной иммунной реакции, особенно в ответ на вирусные инфекции. В частности, IRF5 был определен как ген микроглийного риска, связанный с множественным склерозом (MS), однако его конкретная роль в патогенезе MS остается неясной. С помощью ирф5-/- мышей наше исследование обнаруживает неканоническую функцию IRF5 в восстановлении MS. Ирф5-/- мыши продемонстрировали повышенный ущерб в экспериментальной модели аутоиммунной энцефаломиелита (EAE) и продемонстрировали неисправный набор

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… Specifically, in IRF5-deficient microglia, there were significant reductions in the concentrations of various phospholipid families, including plasmalogens and phosphatidylinositols (Fig. 7 B). … B Histograms showing the concentration of different plasmalogens, phosphatidylinositols and cholesterol esters in WT and Irf5 -/- microglia, after 48 hours of myelin challenge. Data are presented as means for every lipid species from 4 independent experiments. …

Спасение гиппокампальной синаптической пластичности и эффективности памяти Финголимода (FTY720) в модели APP/PS1 болезни Альцгеймера сопровождается коррекцией метаболизма финголипидов, полиаминов и фосфолипидного насыщенного состава.

Ранее, наши метаболомические, транскриптомные и геномные исследования характеризовали путь церамида/шфингомилена как терапевтическую цель в болезни Альцгеймера, и мы показали, что FTY720, фингозин-1-фосфахатный рецептор, утвержденный для лечения множественных склерозов, восстанавливает синаптическая пластичность и память в мышах APP/PS1. Для дальнейшего изучения того, как FTY720 спасает патологию, мы провели метаболический анализ мозга, плазмы и печени обученных APP/PS1 и диких мышей. APP/PS1 мыши продемонстрировали локальные нарушения мозга в полиаминах, фосфолипидах и сфинголипидах. Большинс

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… Similarly strong normalization was apparent in ratios with MUFA, PUFA, and SFA phospholipids in temporal cortex (MUFA/SFA and PUFA/MUFA phosphatidylethanolamines (PEs), PUFA/SFA PE plasmalogens, PUFA/MUFA phosphatidylglycerols (PGs), and PUFA/MUFA phosphatidylserines (PSs)). … The shift in the balance of PE synthesis pathways is then likely further reflected in the observed altered composition of LPEs and (L)PE plasmalogens, as they partake in the PE regulatory mechanism 67 , 68 . …

Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing.

Among various organs, in the brain, the fatty acids most extensively studied are omega-3 fatty acids. Alpha-linolenic acid (18:3omega3) defi … eing, predominantly associated with a reduction of phosphatidylethanolamines (mainly in the form of plasmalogens). Peroxisomal oxidation of polyunsaturated fatty acids decreases in the brain during ageing, participating in decreased turnover of membrane fatty acids, which are also less effectively protected against peroxidation by free radicals.

Impact of Alterations in Homocysteine, Asymmetric Dimethylarginine and Vitamins-Related Pathways in Some Neurodegenerative Diseases: A Narrative Review.

Hyperhomocysteinemia (HHcy) influences the development and progression of neurodegenerative disorders in different ways. Homocysteine (Hcy) metabolism is related to that of asymmetric dimethylarginine (ADMA) and group B vitamins. The breakdown of the pathway involving nitric oxide (NO) and ADMA can be considered one of the causes of endothelial alteration that represents a crucial step in the development of several neurodegenerative disorders. Deficiencies of vitamins other than group B ones, such as D and A, have also been associated with central nervous system disorders. The aim of this narr

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… In this trial, the treatment with vitamin B12, consisting of one injection of 10 mg vitamin B12, was associated with an increment in the metabolic markers involved in myelin integrity and membrane dynamics, such as plasmalogens that are ether phospholipids involved in PD and other neurological disorders …