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The circadian clock sets a spatial-temporal window for recent thymic emigrants.

The diurnal timing system regulates multiple functions of lymphocytes in peripheral lymphoid organs. Whether T-cell development in the thymu … erivascular space of the thymus, exhibited robust circadian oscillations. The diurnal expression of sphingosine-1-phosphate receptor-1 (S1PR1) and CCR2 on SP thymocytes and the rhythmic sphingosine-1-phosphate (S1P) and CCL2 gradient formed between peripheral blood and thymus likely promoted SP thymocyte egress in a circadian pattern. Switching the daylight c …

Neutral ceramidase deficiency protects against cisplatin-induced acute kidney injury.

Cisplatin is a commonly used chemotherapeutic for the treatment of many solid organ cancers; however, its effectiveness is limited by the development of acute kidney injury (AKI) in 30% of patients. AKI is driven by proximal tubule cell death, leading to rapid decline in renal function. It has previously been shown that sphingolipid metabolism plays a role in regulating many of the biological processes involved in cisplatin-induced AKI. For example, neutral ceramidase (nCDase) is an enzyme responsible for converting ceramide into sphingosine, which is then phosphorylated to become sphingosine-…

S1P-Induced TNF-α and IL-6 Release from PBMCs Exacerbates Lung Cancer-Associated Inflammation.

Sphingosine-1-phosphate (S1P) is involved in inflammatory signaling/s associated with the development of respiratory disorders, including cancer. However, the underlying mechanism/s are still elusive. The aim of this study was to investigate the role of S1P on circulating blood cells obtained from healthy volunteers and non-small cell lung cancer (NSCLC) patients. To pursue our goal, peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with S1P. We found that the administration of S1P did not induce healthy PBMCs to release pro-inflammatory cytokines. In sharp contrast, S1P …

Sphk2 deletion is involved in structural abnormalities and Th17 response but does not aggravate colon inflammation induced by sub-chronic stress.

The chronic inflammatory process that characterizes inflammatory bowel diseases (IBD) is mainly driven by T-cell response to microbial and environmental antigens. Psychological stress is a potential trigger of clinical flares of IBD, and sphingosine-1-phosphate (S1P) is involved in T-cell recruitment. Hence, stress impact and the absence of sphingosine kinase 2 (Sphk2), an enzyme of S1P metabolism, were evaluated in the colon of mice after sub-chronic stress exposure. Here, we show that sub-chronic stress increased S1P in the mouse colon, possibly due to a decrease in its degradation enzymes a…

Integrated transcriptomic analysis of human tuberculosis granulomas and a biomimetic model identifies therapeutic targets.

Tuberculosis (TB) is a persistent global pandemic, and standard treatment for it has not changed for 30 years. Mycobacterium tuberculosis (M … thways with human disease and identified 12 intracellular enzymes as potential therapeutic targets. Sphingosine kinase 1 inhibition controlled Mtb growth, concurrently reducing intracellular pH in infected monocytes and suppressing inflammatory mediator secretion. Immunohistochemical staining confirmed that sphingosine kinase 1 is expressed in human lung TB g …

Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation.

Cathepsin K (CTSK) is secreted by osteoclasts to degrade collagen and other matrix proteins during bone resorption. Global deletion of Ctsk … ing that the increased BFR is osteoclast dependent. Deletion of Ctsk in osteoclasts increased their sphingosine kinase 1 (Sphk1) expression. Conditioned media from Ctsk-deficient osteoclasts, which contained elevated levels of sphingosine-1-phosphate (S1P), increased alkaline phosphatase and mineralized nodules in osteoblast cultures. An S1P1,3 receptor antag …

Cerebrospinal fluid metabolomics in autistic regression reveals dysregulation of sphingolipids and decreased β-hydroxybutyrate.

BACKGROUND: Autism is highly heritable, however actionable genetic findings are only found in a minority of patients. Many people with autis … ession, and the findings were validated using a targeted β-hydroxybutyrate assay. The sphingolipid, sphingosine-1-phosphate was significantly elevated in the discovery case-control studies, and sphingolipid metabolism pathways were also significantly dysregulated. We therefore developed a targeted metabolite assay of forty sphingolipids. After FDR correction, …

[Mechanism of Jingangteng Capsules in ameliorating chronic nonbacterial prostatitis based on gut microbiota and metabolomics].

Based on the experimental autoimmune prostatitis(EAP) rat model, this study investigated the effects and mechanisms of Jingangteng Capsules( … of JGTCs in ameliorating CNP. Western blot(WB) was utilized to validate the effects of JGTCs on the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate receptor 1(S1P1)/phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) pathway. The results show that JGTCs can ameliorate pathological injury of the prostate, enhance the density of lecithin bodies, reduc …

Comprehensive Metabolic Profiling of Brucea javanica Oil Oral Emulsion in Rat Serum by Ultrahigh Performance Liquid Chromatography Time-of-Flight Mass Spectrometry and Its Correlation With Anti-Glioblastoma Activity.

Brucea javanica oil oral emulsion (BJOE) serves as an adjunctive therapeutic agent for glioblastoma multiforme (GBM); however, the inhibitor … id-M1, linoleic acid-M2, linoleic acid-M3, oleic acid, oleic acid-M1, oleic acid-M2, oleic acid-M3, sphingosine, palmitoleic acid, oleamide, and 1-stearoyl-rac-glycerol. Rat serum collected 2 h postdosing significantly inhibited U251 cell proliferation. Gray relationship analysis indicated that oleic acid, oleic acid-M1, linoleic acid, linoleic acid-M1, linol …

Metabolites disorders are associated with the severity of pathological lung injury in patients with concurrent diabetes and tuberculosis: a cross sectional study.

BACKGROUND: Type 2 diabetes mellitus elevates the risk of developing tuberculosis, posing a substantial challenge to TB treatment and contro … ng DM-TB from TB patients. Multivariable logistic regression analysis suggested, high levels of C18 Sphingosine (OR = 2.207, 95% CI = 1.049-4.645), L-Saccharopine (OR = 4.407, 95% CI = 1.045-18.582) and arachidonic acid (AA) (OR = 2.845, 95% CI = 1.272-6.366) were associated with an increased risk of extensive lung lesions. In addition, C18 Sphingosine (OR = …

Pain outcomes in persons with multiple sclerosis receiving S1PR modulators: a cross-sectional study.

BACKGROUND: The impact of disease-modifying therapies (DMTs) on chronic pain in multiple sclerosis (MS) is poorly understood. Preclinical research suggests that modulation of sphingosine-1-phosphate pathways involved in inflammation and central sensitization could exert analgesic effects alongside MS relapse prevention, but more clinical data are needed. OBJECTIVE: To compare pain phenotypes, severity, and treatment regimens in persons living with MS using sphingosine-1-phosphate receptor (S1PR) modulators versus other DMTs. METHODS: We conducted a secondary analysis of cross-sectional data …

Нейропзащитный перекресток из витамина B12 и сфинголипидных сигнальных путей в терапии для множественного склероза.

Множественный склероз (MS) — иммунопосредованное демиелинизирующее заболевание центральной нервной системы (CNS), характеризующееся нейроинфламмацией, обезвоживанием и нейродегенерацией. Что касается методов лечения, направленных на изменение заболеваний, то было доказано, что такие модуляторы, как фингозин 1-фосфат (S1P) рецептор (S1PR), как финголимод, также известный под названием FTY720, оказывают терапевтическое воздействие в результате непосредственных действий CNS в рамках S1PR (например. S1P1), выраженный астроцитами, помимо первоначально предложенного механизма связывания лимфоцитов.

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) characterized by neuroinflammation, demyelination, and neurodegeneration. Among disease-modifying therapies, sphingosine 1-phosphate (S1P) receptor (S1PR) modulators such as fingolimod, also known as FTY720, have been shown to exert therapeutic effects thr…

Serum biomarkers associated with health impacts of high residential radon exposure: a metabolomic pilot study.

Long-term epidemiological evidence suggests that populations exposed to high natural radiation levels for extended periods may have an incre … ) highlighted 12 key candidates associated with high radon exposure. KEGG pathway analysis linked D-sphingosine to lung cancer development and 3-methylhistidine to kidney disease, early preeclampsia, and Alzheimer's disease. These findings suggest that D-sphingosine and 3-methylhistidine are promising serum biomarkers for identifying high-risk individuals wit …

Circular Network of Coregulated Sphingolipids Dictates Chronic Hypoxia Damage in Patients With Tetralogy of Fallot.

Background: Tetralogy of Fallot (TOF) is the most common cyanotic heart disease. However, the association of cardiac metabolic reprogramming … sm were identified. We found that four core genes, UDP-Glucose Ceramide Glucosyltransferase (UGCG), Sphingosine-1-Phosphate Phosphatase 2 (SGPP2), Fatty Acid 2-Hydroxylase (FA2H), and Sphingosine-1-Phosphate Phosphatase 1 (SGPP1), were downregulated in TOF. Conclusion: Sphingolipid metabolism was downregulated in TOF; however, the detailed mechanism needs fur …

Efficacy of AAV9-mediated SGPL1 gene transfer in a mouse model of S1P lyase insufficiency syndrome.

Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a rare metabolic disorder caused by inactivating mutations in sphingosine-1-phosphate lyase 1 (SGPL1), which is required for the final step of sphingolipid metabolism. SPLIS features include steroid-resistant nephrotic syndrome and impairment of neurological, endocrine, and hematopoietic systems. Many affected individuals die within the first 2 years. No targeted therapy for SPLIS is available. We hypothesized that SGPL1 gene replacement would address the root cause of SPLIS, thereby serving as a universal treatment for the condit…

Neurodegeneration Caused by S1P-Lyase Deficiency Involves Calcium-Dependent Tau Pathology and Abnormal Histone Acetylation.

We have shown that sphingosine 1-phosphate (S1P) generated by sphingosine kinase 2 (SK2) is toxic in neurons lacking S1P-lyase (SGPL1), the enzyme that catalyzes its irreversible cleavage. Interestingly, patients harboring mutations in the gene encoding this enzyme (SGPL1) often present with neurological pathologies. Studies in a mouse model with a developmental neural-specific ablation of SGPL1 (SGPL1fl/fl/Nes) confirmed the importance of S1P metabolism for the presynaptic architecture and neuronal autophagy, known to be essential for brain health. We now investigated in SGPL1-deficient murin…

Advances in the management of peritoneal mesothelioma.

Malignant peritoneal mesothelioma (PM) is an infrequent disease which has historically been associated with a poor prognosis. Given its long … ifying molecular targets and developing targeted therapies is emerging. Among such novel targets is sphingosine kinase 1 (SphK1) which regulates the production of sphingosine-1-phosphate, a biologically active lipid implicated in various cancers including malignant mesothelioma. The known action of specific SphK inhibitors may warrant further exploration in p …

Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural characterization and immunoreactivity in cerebrospinal fluid.

Fast migrating cerebrosides (FMC) are derivatives of galactosylceramide (GalCer). The structures of the most hydrophobic FMC-5, FMC-6, and FMC-7 were determined by electrospray ionization linear ion-trap mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy complementing previous NMR spectroscopy and gas chromatography-mass spectrometry to be 3-O-acetyl-sphingosine-GalCer derivatives with galactose O-acetyl modifications. FMC-5 and FMC-6 are 3-O-acetyl-sphingosine-2,3,4,6-tetra-O-acetyl-GalCer with nonhydroxy and hydroxy-N-fatty-acids, while FMC-7 has an additional O-acetyla…

Sphk1 and Sphk2 Differentially Regulate Erythropoietin Synthesis in Mouse Renal Interstitial Fibroblast-like Cells.

Erythropoietin (Epo) is a crucial hormone regulating red blood cell number and consequently the hematocrit. Epo is mainly produced in the kidney by interstitial fibroblast-like cells. Previously, we have shown that in cultures of the immortalized mouse renal fibroblast-like cell line FAIK F3-5, sphingosine 1-phosphate (S1P), by activating S1P1 and S1P3 receptors, can stabilize hypoxia-inducible factor (HIF)-2α and upregulate Epo mRNA and protein synthesis. In this study, we have addressed the role of intracellular iS1P derived from sphingosine kinases (Sphk) 1 and 2 on Epo synthesis in F3-5 ce…

Apparent cortisone reductase deficiency: a rare cause of hyperandrogenemia and hypercortisolism.

Sphingosine kinases (Sphk1/2 EC 2.7.1.91) are responsible for synthesis of sphingosine-1-phosphate (S1P) and for regulation of the bioactive sphingolipids homeostasis. Sphingosine-1-phosphate can act as a potent messenger in an autocrine/paracrine manner through five specific G protein-coupled receptors (GPCR) S1P1-5. This sphingolipid is involved in the mechanism of transcription, mitochondrial function, neuronal viability and degeneration. Until now the involvement of Sphk1/2 and sphingolipid alterations in Parkinson's disease (PD) remains unknown. Recent studies have indicated the role of s…