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Conditional PLD1 deletion or pharmacological PLD inhibition mitigates astrocyte reactivity and promotes functional recovery after spinal cord injury.

AIM: To investigate the effects of pharmacological PLD inhibition and astrocyte-specific PLD1 deletion on functional recovery and tissue pathology after SCI. MAIN METHODS: A contusion SCI model was established in transgenic mice with conditional astrocytic PLD1 deletion, as well as in wild-type animals treated with Five-Fluoro-2-Indolyl Des-Chlorohalopemide (FIPI), a pharmacological PLD inhibitor. Motor function recovery, tissue preservation, and astrocytic activity were assessed. In addition, lipidomic profiling was performed to evaluate metabolic alterations associated with SCI and PLD inhi

Multi-omics profiling in spinal muscular atrophy (SMA): investigating lipid and metabolic alterations through longitudinal CSF analysis of Nusinersen-treated patients.

Spinal muscular atrophy (SMA) is a rare neuromuscular disease caused by biallelic mutations in the SMN1 gene, leading to progressive muscle weakness due to degeneration of the anterior horn cells. Since 2017, SMA patients can be treated with the anti-sense oligonucleotide Nusinersen, which promotes alternative splicing of the SMN2 gene, by regular intrathecal injections. In this prospective study, we applied metabolomic, lipidomic, and proteomic analysis to examine sequential CSF samples from 13 SMA patients and controls. This multi-omic approach identified over 800 proteins and 400 small mole

Phospholipid isotope tracing suggests β-catenin-driven suppression of phosphatidylcholine metabolism in hepatocellular carcinoma.

Activating mutations in the CTNNB1 gene encoding β-catenin are among the most frequently observed oncogenic alterations in hepatocellular carcinoma (HCC). Profound alterations in lipid metabolism, including increases in fatty acid oxidation and transformation of the phospholipidome, occur in HCC with CTNNB1 mutations, but it is unclear what mechanisms give rise to these changes. We employed untargeted lipidomics and targeted isotope tracing to measure phospholipid synthesis activity in an inducible human liver cell line expressing mutant β-catenin, as well as in transgenic zebrafish with activ…

Complex Interplay between Sphingolipid and Sterol Metabolism Revealed by Perturbations to the Leishmania Metabolome Caused by Miltefosine.

With the World Health Organization reporting over 30,000 deaths and 200,000 to 400,000 new cases annually, visceral leishmaniasis is a serious disease affecting some of the world's poorest people. As drug resistance continues to rise, there is a huge unmet need to improve treatment. Miltefosine remains one of the main treatments for leishmaniasis, yet its mode of action (MoA) is still unknown. Understanding the MoA of this drug and parasite response to treatment could help pave the way for new and more successful treatments for leishmaniasis. A novel method has been devised to study the metabo

Photoreceptor outer segments promote the accumulation of lipid droplets in microglia by reprogramming lipid metabolism.

Retinal degeneration (RD) ultimately leads to blindness owing to progressive photoreceptor loss. Previous studies have shown that microglia play a key role in photoreceptor degeneration through multiple phenotypes. However, the determinants of their phenotypic regulation remain unclear. As microglia migrate into the subretinal space and engulf photoreceptor outer segments (POSs), we aim to investigate how POSs affect microglial activation and the relevant pathways. A classic mouse microglial cell line (BV2) was used to explore the effect of POS exposure on microglia activation. Transcriptomic

Impact of APOE on cerebrovascular lipid profile in Alzheimer's disease.

Disturbances within the cerebrovascular system substantially contribute to the pathogenesis of age-related cognitive impairment and Alzheime … brovascular lipid signatures in AD brains remains unclear. In this study, we conducted non-targeted lipidomics on cerebral vessels isolated from the middle temporal cortex of 89 postmortem human AD brains, representing varying degrees of CAA and different APOE genotypes: APOE ε2/ε3 (N = 9), APOE ε2/ε4 (N = 14), APOE ε3/ε3 (N = 21), APOE ε3/ε4 (N = 23), and A …

Comprehensive Metabolomics Identified the Prominent Role of Glycerophospholipid Metabolism in Coronary Artery Disease Progression.

Background: Coronary stenosis severity determines ischemic symptoms and adverse outcomes. The metabolomic analysis of human fluids can provide an insight into the pathogenesis of complex disease. Thus, this study aims to investigate the metabolomic and lipidomic biomarkers of coronary artery disease (CAD) severity and to develop diagnostic models for distinguishing individuals at an increased risk of atherosclerotic burden and plaque instability. Methods: Widely targeted metabolomic and lipidomic analyses of plasma in 1,435 CAD patients from three independent centers were performed. These pati

Selective Protein and Lipid Cargo Sorting into Extracellular Vesicles of Lacticaseibacillus paracasei subsp. paracasei.

Extracellular vesicles (EVs) are nanoscale lipid bilayer particles that transport bioactive cargo. EVs from lactic acid bacteria show health benefits and drug-delivery potential, yet cargo encapsulation remains understudied. Here, EVs were isolated, purified, and characterized from the bacteriocin-producing strain Lacticaseibacillus paracasei subsp. paracasei YCL29, which was isolated from fermented Yucha. Proteomic and lipidomic analyses were subsequently conducted to compare the EVs with their parental L. paracasei YCL29 cells. Nanoflow cytometry indicated EVs with mean diameter 86.0 ± 18.8 

Novel Extended Tetraether Lipids Found in a High-CO2 Geyser.

The growing research into the archaeal lipidome has uncovered a remarkable structural diversity in isoprenoidal glycerol dialkyl glycerol tetraethers (iGDGTs) and revealed complex membrane adaptations, especially in extreme environments. We performed a comprehensive analysis of the lipidome from the subsurface aquifer of the CO2-rich, cold-water Geyser Andernach (Germany), using ultra-high-resolution mass spectrometry. We detected iGDGT-0, presumably derived from the dominant community member Candidatus Altiarchaeum, providing supporting evidence for its ability to synthesise tetraethers, as p

Мозговые липидные метаболизмы и перенос: последствия для нейродегенерации и терапевтических стратегий: всеобъемлющий обзор.

В этом всеобъемлющем обзоре 2024 года рассматриваются ключевые функции липидов в неврологическом здоровье, а также подчеркивается их жизненно важный вклад в структуру, функцию и патологию мозга. Сложный липидный состав мозга, состоящий из фосфолипидов, шпинголипидов, холестерина, гликолипидов и полиненасыщенных жирных кислот, поддерживает целостность мембран, синаптическую трансмиссию и миелинацию. Производство липидов, метаболизм и перенос в центральной нервной системе тщательно контролируются, что требует специализированного взаимодействия между нейронами, глиарными клетками и мозговым барье

Совпадение в аннотации оригинала
This 2024comprehensive review examines the crucial functions of lipids in neurological health, highlighting their vital contributions to bra … yunsaturated fatty acids, which regulate neuroinflammation and enhance neuroprotection. Progress in lipidomics has enabled the discovery of new lipid biomarkers and therapeutic targets, presenting intriguing opportunities for disease diagnosis, prognosis, and therapy. This paper highlights the significance of lipid biology in maintaining brain health and the …

Mycogenic Silver Nanoparticles: Promising Antimicrobials with Fungistatic Properties.

The antimicrobial activity of silver nanoparticles (AgNPs) makes them a valuable tool in various industries. Recently, biosynthesis has become the preferred method for nanoparticle synthesis, and among organisms that can be used as AgNP producers, filamentous fungi have attracted the greatest interest. In particular, wood decay fungi are considered promising candidates for AgNP biosynthesis. Biogenic AgNPs have been proven to have strong antibacterial potential and antifungal activity. The aim of this study was to evaluate the antifungal potential of AgNPs synthesized using the brown-rot decay

Hyperbaric Oxygen Improves Cognitive Impairment Induced by Hypoxia via Upregulating the Expression of Oleic Acid and MBOAT2 of Mice.

Cognitive impairment (CI) causes severe impairment of brain function and quality of life of patients, which brings a great burden to society. Cerebral hypoxia is an important factor in the pathogenesis of CI. Hyperbaric oxygen (HBO) therapy may mitigate hypoxia-induced CI, but its efficacy and mechanisms are not fully understood. In this study, a mice model of CI induced by hypoxia environment was established, then behavioral tests, pathological examination, metabolomic and lipidomic analyses, and molecular biology were used to assess the impact of HBO on hypoxia-induced CI. HBO was found to a

Sub-chronic exposure to hexaconazole affects the lipid metabolism of rats through mTOR-PPAR-γ/SREBP1 signaling pathway mediated by oxidative stress.

Hexaconazole (Hex) is a widely used and high frequency detected triazole fungicide in agricultural products and environment which may pose potential toxicity to the nontargeted organisms. Hex had been reported to affect lipid homeostasis while the mechanism was undefined. This study aims to explore the characteristic lipidomic profiles and clarify the underlying signaling pathways of Hex-induced lipid metabolism disorder in rat liver. The results showed that sub-chronic exposure to environmental related concentrations of Hex caused histopathological changes, oxidative stress, fat accumulation,

Plasma Lipid Profiling Contributes to Untangle the Complexity of Moyamoya Arteriopathy.

Moyamoya arteriopathy (MA) is a rare cerebrovascular disorder characterized by ischemic/hemorrhagic strokes. The pathophysiology is unknown. A deregulation of vasculogenic/angiogenic/inflammatory pathways has been hypothesized as a possible pathophysiological mechanism. Since lipids are implicated in modulating neo-vascularization/angiogenesis and inflammation, their deregulation is potentially involved in MA. Our aim is to evaluate angiogenic/vasculogenic/inflammatory proteins and lipid profile in plasma of MA patients and control subjects (healthy donors HD or subjects with atherosclerotic c

Identification of Circulating Endocan-1 and Ether Phospholipids as Biomarkers for Complications in Thalassemia Patients.

Despite advances in our knowledge and attempts to improve therapies, β-thalassemia remains a prevalent disorder with increased risk for the development of cardiomyopathy. Using an untargeted discovery-based lipidomic workflow, we uncovered that transfusion-dependent thalassemia (TDT) patients had a unique circulating lipidomic signature consisting of 387 lipid features, allowing their significant discrimination from healthy controls (Q-value < 0.01). In particular, TDT patients had elevated triacylglycerols and long-chain acylcarnitines, albeit lower ether phospholipids or plasmalogens, sphing

AOAH remodels arachidonic acid-containing phospholipid pools in a model of interstitial cystitis pain: A MAPP Network study.

Interstitial cystitis/bladder pain syndrome (IC) is a debilitating condition of chronic pelvic pain with unknown etiology. Recently, we used … trate for AOAH. Here, we quantified the effects of AOAH on phospholipids containing AA. Spinal cord lipidomics revealed increased AA-containing phosphatidylcholine in AOAH-deficient mice and concomitantly decreased AA-phosphatidylethanolamine, consistent with decreased CoA-independent transferase activity (CoIT). Overexpression of AOAH in cell cultures simil …

Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia.

CTP:phosphoethanolamine cytidylyltransferase (ET), encoded by PCYT2, is the rate-limiting enzyme for phosphatidylethanolamine synthesis via … s in patient fibroblasts impacting both neutral etherlipid and etherphospholipid metabolism. Plasma lipidomics studies also identified changes in etherlipids that have the potential to be used as biomarkers for ET deficiency. In conclusion, our data establish PCYT2 as a disease gene for a new complex hereditary spastic paraplegia and confirm that etherlipid …

Plasma lipid profiles discriminate bacterial from viral infection in febrile children.

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection prod

Obesity Amplifies the Detrimental Effects of Delayed Repair on Tendon-to-Bone Healing After Rotator Cuff Injury in a Rat Model.

BACKGROUND: Rotator cuff repair outcomes are influenced by systemic metabolic status and tear chronicity. Although obesity and delayed surge … resonance imaging (MRI), gait analysis, and histology/immunofluorescence; biomechanical testing and lipidomics were performed at 8 weeks. RESULTS: Across assessments, delayed repair was associated with impaired recovery, and obesity exacerbated these effects, yielding worse outcomes. Specifically, the combined condition exhibited a more unfavorable MRI appe …

Systemic lipid remodeling associated with deferoxamine treatment, dietary intervention and combinatorial effect in ameliorating high cholesterol diet-induced steatotic liver in mice.

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming increasingly more prevalent and poses a major gro … lipin staining, iron assay, inflammatory marker measurements and utilized multi-omics technologies (lipidomics and proteomics using mass spectrometers) to interrogate MASLD. RESULTS: Comprehensive lipidomics analysis revealed that elevated GM3 levels resulting in abnormal lipid metabolism in the HCD-fed mice decreased after DFO treatment and dietary interve …