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A Lipidomics Approach to Assess the Association Between Plasma Sphingolipids and Verbal Memory Performance in Coronary Artery Disease Patients Undertaking Cardiac Rehabilitation: A C18:0 Signature for Cognitive Response to Exercise.

BACKGROUND: Early subtle deficits in verbal memory, which may indicate early neural risk, are common in patients with coronary artery disease (CAD). While exercise can improve cognition, cognitive response to exercise is heterogeneous. Sphingolipids have been associated with the development and progression of CAD, and impairments in sphingolipid metabolism may play roles in neurodegeneration and in the neural adaptation response to exercise. OBJECTIVE: In this study, change in plasma concentrations of sphingolipids was assessed in relation to change in verbal memory performance and in other c

Sphingolipid metabolism correlates with cerebrospinal fluid Beta amyloid levels in Alzheimer's disease.

Sphingolipids are important in many brain functions but their role in Alzheimer's disease (AD) is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF) contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant f

Human endothelial cell activation and mediator release in response to Listeria monocytogenes virulence factors.

The interaction of Listeria monocytogenes with endothelial cells represents a crucial step in the pathogenesis of listeriosis. Incubation of human umbilical vein endothelial cells (HUVEC) with wild-type L. monocytogenes (EGD) provoked immediate strong NO synthesis, attributable to listerial presentation of listeriolysin O (LLO), as the NO release was missed upon employment of a deletion mutant for LLO (EGD hly mutant) and was reproduced by purified LLO. Studies of conditions lacking extracellular Ca(2+) suggested LLO-elicited Ca(2+) flux as the underlying mechanism. In addition, HUVEC incubati

Lipotoxicity Disrupts Erythrocyte Function: A Perspective.

BACKGROUND: Lipid accumulation in the liver, skeletal and cardiac muscle, kidneys and pancreas causes cell dysfunction, death and inflammation, a biological phenomenon named lipotoxicity. Erythrocytes participate in the transport of lipids in the circulation, and their lipidome is determined by exchange with blood components. OBJECTIVE: The objective of this study is to summarize the current knowledge regarding the effect of toxic lipid accumulation in erythrocytes. RESULTS: Erythrocyte lipidome is altered in lipotoxic diseases, such as fatty liver disease, heart failure and diabetes. In add

Orosomucoid-like protein 3, rhinovirus and asthma.

The genetic variants of orosomucoid-like protein 3 (ORMDL3) gene are associated with highly significant increases in the number of human rhinovirus (HRV)-induced wheezing episodes in children. Recent investigations have been focused on the mechanisms of ORMDL3 in rhinovirus infection for asthma and asthma exacerbations. ORMDL3 not only regulates major human rhinovirus receptor intercellular adhesion molecule 1 expression, but also plays pivotal roles in viral infection through metabolisms of ceramide and sphingosine-1-phosphate, endoplasmic reticulum (ER) stress, ER-Golgi interface and glycoly

Miglustat: substrate reduction therapy for glycosphingolipid lysosomal storage disorders.

Substrate reduction therapy offers a novel approach to the treatment of lysosomal storage disorders. By reducing the rate of macromolecule synthesis to a level where the residual degradative activity in the cell is sufficient to prevent substrate accumulation, it should be possible to reverse storage and storage-related pathologies. Miglustat is an N-alkylated imino sugar that acts against a number of enzymes involved in processing glycoconjugates, including the ceramide-specific glucosyltransferase, which catalyzes the initial committed step in glycosphingolipid synthesis. Miglustat could the

Saposins (sap) A and C activate the degradation of galactosylsphingosine.

As previously shown for [(3)H-galactosyl]ceramide, the breakdown of [(3)H-galactosyl]sphingosine was reduced in prosaposin-deficient skin fibroblast homogenates. Galactosylsphingosine hydrolysis was also deficient in cell homogenates from Krabbe's disease (beta-galactocerebrosidase-deficient) patients, but not acid beta-galactosidase-deficient patients. Moreover, hydrolysis of galactosylsphingosine in the prosaposin-deficient cell homogenates could be partially restored by adding pure saposin A or C, thereby identifying these saposins as essential facilitators of galactosylsphingosine hydrolys

Monoclonal anti-type 2 H: an antibody detecting a precursor of the A and B blood group antigens.

A monoclonal antibody was produced which binds specifically to Type 2 H antigen of the ABO blood group system. The antibody, H11, is an IgM molecule which reacts by direct agglutination of red cells with the same pattern as other anti H reagents such as Ulex europaeus lectin. The specificity was determined by inhibition and adsorption with chemically defined oligosaccharides. H11 also reacted with poly (glycosyl) ceramide purified from group 0 red cells and glycoprotein H purified from human stomach mucosa and meconium. H11 differs from Ulex lectin, however, in that it was not inhibited by sal

Mechanisms and Repair of Skin Barrier Dysfunction: The TLC Strategy.

The skin barrier functions as a key line of defense with physical, chemical, microbial, and immunological components that act synergistically to protect the body against extrinsic antigens, microbes, and ultraviolet rays and prevent loss of nutrients and moisture from the body. Skin barrier dysfunction is caused by various factors, including environmental stressors, genetic predisposition, psychological stress, and inadequate nutrition. These factors can lead to metabolic, immunological, and microbial disorders of the skin barrier, which are associated with skin diseases, such as sensitive ski

The role of dihydrosphingolipids in disease.

Dihydrosphingolipids refer to sphingolipids early in the biosynthetic pathway that do not contain a C4-trans-double bond in the sphingoid backbone: 3-ketosphinganine (3-ketoSph), dihydrosphingosine (dhSph), dihydrosphingosine-1-phosphate (dhS1P) and dihydroceramide (dhCer). Recent advances in research related to sphingolipid biochemistry have shed light on the importance of sphingolipids in terms of cellular signalling in health and disease. However, dihydrosphingolipids have received less attention and research is lacking especially in terms of their molecular mechanisms of action. This is de

The sperm survival switch: circRNA-mediated regulatory loops control apoptotic signalling in human spermatozoa.

Male reproductive health is declining worldwide, partly due to lifestyle factors including obesity, which is linked to increased sperm apoptosis and impaired assisted reproductive technologies (ARTs) outcomes. This growing issue underscores the urgent need for novel molecular biomarkers capable of improving sperm quality assessment. In this context, circular RNAs (circRNAs) are emerging as regulators of germ cell functions and apoptosis, but their role as early apoptotic markers in human sperm under lifestyle-related stress remains poorly explored. In this study, by using the obesity as experi

Association Between Human Milk-Targeted Metabolites and Maternal Characteristics: Targeted Metabolomic Profiling of Human Milk in Low-Income Settings.

Background/Objectives: Human milk (HM) is recognized as the optimal source of infant nutrition, particularly during the first six months of … , and small molecules including amino acids (26.67%), amino acid-related compounds (21.33%), hexosylceramides (17.33%), and fatty acids (14.67%). Maternal age was positively correlated with a wide range of metabolites, mainly cholesteryl esters, sphingomyelins, triglycerides, and acylcarnitines, while child age was associated with metabolites belonging to a …

LASS2 alleviates liver fibrosis by interacting with THBS1, TFRC, and APOE to inhibit TGF-β1 signaling and ferroptosis, and by reshaping the hepatocyte lipid secretome to suppress paracrine HSC activation.

BACKGROUND: Liver fibrosis (LF) lacks effective therapies. Longevity assurance homolog 2 (LASS2), a key ceramide synthase, contributes to li … ized by downregulation of pro-fibrotic lysophospholipids (LPC/LPE/LPI), phosphatidic acid (PA), and ceramides (Cer), alongside upregulation of specific sphingomyelin (SM) and BMP species, creating an anti-fibrotic paracrine milieu. CONCLUSIONS: LASS2 acts as a dual-function metabolic-signaling integrator: it directly engages THBS1, TFRC, and APOE to contro …

Profile of the Main Representatives of Sphingolipid Metabolism in the Maxillary and Mandibular Periosteum of Patients with Dentofacial Deformities After Osteosynthesis Using Titanium Implants.

Background/Objectives: The objective of this study was to analyze the profiles of sphingosine (Sph), sphinganine (SPA), sphingosine-1-phosphate (S1P), and ceramides (C14 Cer, C16 Cer, C18:1 Cer, C18 Cer, C20 Cer, C22 Cer, C24:1 Cer, and C24 Cer), along with caspases (CAS-3, CAS-6, and CAS-9), in serum and in the periosteum of the maxilla and mandible in patients with dentofacial deformities undergoing treatment with titanium fixations (miniplates and miniscrews). Methods: The study group comprised 20 patients who underwent bilateral jaw osteotomy due to dentofacial deformities. The osteotomy s…

Short-Term Acid Sphingomyelinase Deficiency Exerts Proinflammatory and Antiapoptotic Effects during LPS-induced Lung Injury in Mice.

Lysosomal acid sphingomyelinase (ASM; SMPD1) deficiency causes Niemann-Pick disease that, in type B, manifests with interstitial lung disease and susceptibility to infections. Constitutional Smpd1 (Smpd1-/- mouse) deletion causes lung inflammation with foamy dysfunctional macrophages but is protective against acute lung injury. It is unknown whether these manifestations are a result of progressive accumulation of sphingomyelin, decreased ceramide, or compensatory alterations in sphingolipid metabolism. We developed a conditional knockout mouse, CAGG-CreERTM × Smpd1fl/fl, induced by tamoxifen (

Profiling lipidomic variations in primary open-angle and angle-closure glaucoma patients.

Retinal ganglion cell death in glaucoma leads to progressive and irreversible vision loss. Investigating lipidomic profiles of aqueous humor … es (>50 %) were elevated in aqueous humor of both glaucoma groups, while sphingomyelins (>85 %) and ceramides (18.75 %) were specifically elevated in PACG. Of 301 lipid species identified in aqueous humor, 51 met significance (POAG: 24, PACG: 27). In plasma, diglycerides (>20 %), triglycerides and cholesterol esters (>10 %, log2FC ≤ -1) were declined in bot …

Серум Lipid Profile replaping multical Sclerosis Differs излечивается от здорового контроля.

Биомаркеры крови, которые коррелируют с воспалительным демиэлированием или нейродегенерацией, необходимы для ранней диагностики и мониторинга заболеваний при множественном склерозе (MS). Цель этого исследования состояла в том, чтобы выявить липиды сыворотки, которые воспроизводимо изменяются при повторном производстве эмиссий MS (RRMS) и соотносятся с показателями серьезности заболеваний. Липиды были подсчитаны с использованием жидкой хроматографии-тандем масс-спектрометрии в когорте открытия 47 RRMS, 42 других неврологических расстройств и 30 здоровых образцов контрольной сыворотки, а также в

Совпадение в аннотации оригинала
Blood biomarkers that correlate with inflammatory demyelination or neurodegeneration are needed for early diagnosis and disease monitoring i … rt). Three acylcarnitines, one brain-enriched ceramide (d18:1/18:0), and two myelin-enriched hexosylceramides were positively correlated with EDSS scores in the validation cohort, of which two were also correlated with MSSS scores. However, these associations were not observed in the discovery cohort. The neuron-enriched lipid SM(d18:1/18:0) was significant …

Alirocumab and Lipid Levels, Inflammatory Biomarkers, Metabolomics, and Safety in Patients Receiving Maintenance Dialysis: The ALIrocumab in DIALysis Study (A Phase 3 Trial to Evaluate the Efficacy and Safety of Biweekly Alirocumab in Patients on a Stable Dialysis Regimen).

RATIONALE & OBJECTIVE: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab is used in the general population to t … . The levels of inflammatory biomarkers were not clearly decreased by alirocumab, but the levels of ceramides, sphingomyelins, and cholesterol esters were significantly reduced. TRIAL REGISTRATION: Clinical Trials.gov as NCT03480568.

Variations in hepatic lipid species of age-matched male mice fed a methionine-choline-deficient diet and housed in different animal facilities.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a common disease and feeding mice a methionine-choline-deficient (MCD) diet is a frequen … dietary groups. Cholesterol contributes to hepatic injury but was only elevated in WT2 NASH liver. Ceramides account for insulin resistance and cell death, and ceramide species d18:1/16:0 and d18:1/18:0 were higher in the NASH liver of both groups. Saturated sphingomyelins only declined in WT1 NASH liver. Lysophosphatidylcholine concentrations were quite n …