Exploring Exhaled Breath Analysis in Adults With Chronic Visceral Acid Sphingomyelinase Deficiency to Identify Potential Biomarkers of Pulmonary Involvement.

Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disease. The most commonly affected organs are the spleen, the liver, and the lungs. Pulmonary involvement resembles interstitial lung disease and often leads to decreased diffusion capacity of the lungs for carbon monoxide (DLCO).

Targeting phospholipase PLAG-15 promotes healthy aging in via lysosomal-related genes.

Complex lipid metabolism plays a crucial role in regulating aging. We recently discovered that the phospholipid bis(monoacylglycero)phosphate (BMP) increases in aged human muscles and many mouse tissues. The phospholipase PLA2G15 is reportedly involved in BMP synthesis, however, its specific role in aging remains unknown.

The role of bile salts in itch receptor activation.

Background: Cholestasis-associated pruritus is a distressing symptom. Bile salts and bilirubin are often implicated in the etiology of pruritus. We evaluated whether these compounds activate known itch receptors.

Immuno-metabolic stress responses control longevity from mitochondrial translation inhibition in C. elegans.

Perturbing mitochondrial translation represents a conserved longevity intervention, with proteostasis processes proposed to mediate the resulting lifespan extension. Here, we explore whether other mechanisms may contribute to lifespan extension upon mitochondrial translation inhibition. Using multi-omics and functional in vivo screening, we identify the ethylmalonyl-CoA decarboxylase orthologue C32E8.

Cerebrospinal Fluid Metabolome in Central Nervous System Infections: A Study of Diagnostic Accuracy.

Objective: To assess the diagnostic accuracy of metabolites in cerebrospinal fluid (CSF) for central nervous system (CNS) infections.

Methods: Patients were derived from three prospective cohort studies in the Netherlands. All studies included adults suspected of a CNS infection who underwent a diagnostic lumbar puncture.

Uncovering metabolic pathways in human alveolar macrophages in response to lipopolysaccharide.

Introduction: Alveolar macrophages (AMs) play an essential role in maintaining homeostasis in the lung and in innate immunity for host defense. To fuel inflammatory responses, AMs do not rely on glycolysis, but require oxidative phosphorylation. However, which nutrients AMs use to fuel their energy demand during inflammatory responses, is still unknown.

Small extracellular vesicles from young adipose-derived stem cells ameliorate age-related changes in the heart of old mice.

Background: Aging entails a progressive decline in physiological functions, elevating the risk of age-related diseases like heart failure or aortic stenosis. Stem cell therapies, especially those that use paracrine signaling, can potentially mitigate the adverse effects of aging.

Objectives: The objective is to explore the potential of small extracellular vesicles (sEVs) derived from young adipose-derived stem cells (ADSC-sEVs) in reversing structural, molecular, and functional changes associated with aging in the heart.

Cholesterol homeostasis and lipid raft dynamics at the basis of tumor-induced immune dysfunction in chronic lymphocytic leukemia.

Autologous T-cell therapies show limited efficacy in chronic lymphocytic leukemia (CLL), where acquired immune dysfunction prevails. In CLL, disturbed mitochondrial metabolism has been linked to defective T-cell activation and proliferation. Recent research suggests that lipid metabolism regulates mitochondrial function and differentiation in T cells, yet its role in CLL remains unexplored.

Plasma triacylglycerol length and saturation level mark healthy aging groups in humans.

Complex lipids, essential components in biological processes, exhibit conserved age-related changes that alter membrane properties and cellular functions and are implicated as biomarkers and contributors to longevity and age-related diseases. While physical activity alleviates age-related comorbidities and physical impairments, comprehensive exploration of the underlying biological mechanisms, particularly at the level of complex lipids, remains limited. However, clinical studies suggest that physical activity may counteract these age-related lipidomic changes, presenting a promising avenue for intervention.

Protein Phosphatase 1 Regulatory Subunit 3 Beta rs4240624 Genotype Is Associated With Gallstones and With Significant Changes in Bile Lipidome.

Background And Aims: Gallstone disease (GSD) associates with significant morbidity and mortality. Decreased secretion of bile acids has been suggested as a driving factor for GSD. Recently, we linked the protein phosphatase 1 regulatory subunit 3 beta ( rs4240624 genotype to decreased bile acid levels in bile.

Loss of temporal coherence in the circadian metabolome across multiple tissues during ageing in mice.

Circadian clock function declines with ageing, which can aggravate ageing-related diseases such as type 2 diabetes and neurodegenerative disorders. Understanding age-related changes in the circadian system at a systemic level can contribute to the development of strategies to promote healthy ageing. The goal of this study was to investigate the impact of ageing on 24-h rhythms in amine metabolites across four tissues in young (2 months of age) and old (22-25 months of age) mice using a targeted metabolomics approach.

Four-dimensional lipidomics profiling in X-linked adrenoleukodystrophy using trapped ion mobility mass spectrometry.

Lipids play pivotal roles in an extensive range of metabolic and physiological processes. In recent years, the convergence of trapped ion mobility spectrometry and MS has enabled 4D-lipidomics, a highly promising technology for comprehensive lipid analysis. 4D-lipidomics assesses lipid annotations across four distinct dimensions-retention time, collisional cross section, m/z (mass-to-charge ratio), and MS/MS spectra-providing a heightened level of confidence in lipid annotation.

Smoking cessation only partially reverses cardiac metabolic and structural remodeling in mice.

Aims: Active cigarette smoking is a major risk factor for chronic obstructive pulmonary disease that remains elevated after cessation. Skeletal muscle dysfunction has been well documented after smoking, but little is known about cardiac adaptations to cigarette smoking. The underlying cellular and molecular cardiac adaptations, independent of confounding lifestyle factors, and time course of reversibility by smoking cessation remain unclear.

A conserved complex lipid signature marks human muscle aging and responds to short-term exercise.

Studies in preclinical models suggest that complex lipids, such as phospholipids, play a role in the regulation of longevity. However, identification of universally conserved complex lipid changes that occur during aging, and how these respond to interventions, is lacking. Here, to comprehensively map how complex lipids change during aging, we profiled ten tissues in young versus aged mice using a lipidomics platform.

CIAO1 and MMS19 deficiency: A lethal neurodegenerative phenotype caused by cytosolic Fe-S cluster protein assembly disorders.

Purpose: The functionality of many cellular proteins depends on cofactors; yet, they have only been implicated in a minority of Mendelian diseases. Here, we describe the first 2 inherited disorders of the cytosolic iron-sulfur protein assembly system.

Methods: Genetic testing via genome sequencing was applied to identify the underlying disease cause in 3 patients with microcephaly, congenital brain malformations, progressive developmental and neurologic impairments, recurrent infections, and a fatal outcome.

The shifting lipidomic landscape of blood monocytes and neutrophils during pneumonia.

The lipidome of immune cells during infection has remained unexplored, although evidence of the importance of lipids in the context of immunity is mounting. In this study, we performed untargeted lipidomic analysis of blood monocytes and neutrophils from patients hospitalized for pneumonia and age- and sex-matched noninfectious control volunteers. We annotated 521 and 706 lipids in monocytes and neutrophils, respectively, which were normalized to an extensive set of internal standards per lipid class.

Targeting the ACOD1-itaconate axis stabilizes atherosclerotic plaques.

Inflammatory macrophages are key drivers of atherosclerosis that can induce rupture-prone vulnerable plaques. Skewing the plaque macrophage population towards a more protective phenotype and reducing the occurrence of clinical events is thought to be a promising method of treating atherosclerotic patients. In the current study, we investigate the immunomodulatory properties of itaconate, an immunometabolite derived from the TCA cycle intermediate cis-aconitate and synthesised by the enzyme Aconitate Decarboxylase 1 (ACOD1, also known as IRG1), in the context of atherosclerosis.

Diacylglycerols and Lysophosphatidic Acid, Enriched on Lipoprotein(a), Contribute to Monocyte Inflammation.

Background: Oxidized phospholipids play a key role in the atherogenic potential of lipoprotein(a) (Lp[a]); however, Lp(a) is a complex particle that warrants research into additional proinflammatory mediators. We hypothesized that additional Lp(a)-associated lipids contribute to the atherogenicity of Lp(a).

Methods: Untargeted lipidomics was performed on plasma and isolated lipoprotein fractions.

Ophthalmic acid is a glutathione regulating tripeptide.

Since its discovery in 1958 in the lens of cows, ophthalmic acid (OPH) has stood in the shadow of its anti-oxidant analog: glutathione (GSH). Lacking the thiol group that gives GSH many of its important properties, ophthalmic acid's function has remained elusive, and it has been widely presumed to be an accidental product of the same enzymes. In this review, we compile evidence demonstrating that OPH is a ubiquitous metabolite found in bacteria, plants, fungi, and animals, produced through several layers of metabolic regulation.

The Plasma Lipidomic Landscape in Patients with Sepsis due to Community-acquired Pneumonia.

The plasma lipidome has the potential to reflect many facets of the host status during severe infection. Previous work is limited to specific lipid groups or was focused on lipids as prognosticators. To map the plasma lipidome during sepsis due to community-acquired pneumonia (CAP) and determine the disease specificity and associations with clinical features.