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Role of S1P- and Rho-kinase signalling in age-related myogenic tone deficiency in murine resistance arteries.

Ageing is a risk factor for cardiovascular and neurodegenerative diseases. The myogenic response in resistance arteries is responsible for b … pregulation of P2Y2-R in P2Y6-deficient arteries. MT was not affected in P2Y2-R knock-out mice. The sphingosine-kinase (SK) blocker SKI-II inhibited MT in young mice, and the sphingosine 1-phosphate receptor 2 (S1P2-R) blocker JTE-013 inhibited MT in young and middle-aged mice. MT was impaired in middle-aged mice. Furthermore, MT was reduced in young mice car …

Identification of Plasma Metabolomic Biomarkers of Juvenile Idiopathic Arthritis.

Identification of disease and therapeutic biomarkers remains a significant challenge in the early diagnosis and effective treatment of juven … directional change in both cohorts. JIA was associated with a notable increase in plasma levels of sphingosine metabolites and fatty acid ethanolamides and decreased plasma levels of sarcosine, iminodiacetate, and the unknown metabolite X-12462. Chemical enrichment analysis identified cycloparaffins in the form of naproxen and its metabolites, unsaturated ly …

Воздействие корректирующих болезни методов лечения на результаты беременности при множественном склерозе: перспективное когортное исследование из немецкого реестра множественных склерозов и беременности.

В последние десятилетия повторный перенос множественных склерозов (МС) стал более излечимым с помощью новых методов лечения, направленных на … posure (ИЛИ: 2.16, CI: 1.41, 3.29, значение p: <0.001). Материнская масса значительно сократилась в Sphingosine-1-phosphate-group (β: -132 g, CI: -205, -60, значение p: <0.001) и 3rd-trimester Подгруппа Natalizumab (β: -74 g, CI: -138, -9.4, значение p: 0.02). Небольшие неонатальные лица детородного возраста (СГА) были широко распространены в Sphingosine-1-ph …

Mucosal and Plasma Metabolomes in New-onset Paediatric Inflammatory Bowel Disease: Correlations with Disease Characteristics and Plasma Inflammation Protein Markers.

BACKGROUND AND AIMS: To advance the understanding of inflammatory bowel disease [IBD] pathophysiology, we compared the mucosal and plasma me … CD and UC, mucosal sphingolipids, including ceramide [d18:2/24:1, d18:1/24:2], lactosyl-N-palmitoyl-sphingosine [d18:1/16:0], behenoyl sphingomyelin [d18:1/22:0], lignoceroyl sphingomyelin [d18:1/24:0], and/or sphingomyelin [d18:1/24:1, d18:2/24:0] were increased, correlating with sphingolipids, bile acids, and/or N-acetylated metabolites in plasma. Among pro …

Stratum corneum lipid and cytokine biomarkers at age 2 months predict the future onset of atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) commonly occurs in children and can progress into severe phenotypes or atopic march, causing significant … 001), whereas unsaturated sphingomyelin species (P < .0001) and "short-chain" nonhydroxy fatty acid sphingosine and alpha-hydroxy fatty acid sphingosine ceramides were elevated (P < .01 and .05, respectively) as compared with healthy children. Thymic stromal lymphopoietin and IL-13 levels were increased in the SC of future AD subjects (by 74.5% and 78.3%, P = …

Ocular surface sphingolipids associate with the refractory nature of vernal keratoconjunctivitis: newer insights in VKC pathogenesis.

BACKGROUND: The etiopathogenesis of vernal keratoconjunctivitis (VKC) is incompletely understood. Bioactive lipids play a key role in allerg … ted in the tears by LC-MS/MS analysis. In vitro study was done to assess IgE-induced alterations in sphingosine-1-phosphate (S1P) receptor expression and histone modification in cultured mast cells. RESULTS: Significantly altered gene expression of the sphingolipids enzymes and S1P receptor (SIP3R) were observed in conjunctival imprint cells of VKC cases. Po …

Unique skin abnormality in patients with peanut allergy but no atopic dermatitis.

BACKGROUND: The nonlesional skin of children with atopic dermatitis (AD) with peanut allergy (PA) is associated with increased transepidermal water loss; low urocanic acid (UCA) and pyrrolidone carboxylic acid (PCA), both of which are filaggrin breakdown products; and a reduced ratio of esterified ω-hydroxy fatty acid sphingosine ceramides (EOS-CERs) to nonhydroxy fatty acid sphingosine ceramides (NS-CERs) in the skin. The skin barrier of subjects with PA without AD (AD-PA+) has not been studied. OBJECTIVE: Our aim was to explore whether AD-PA+ is associated with skin barrier abnormalities. …

Glycolipid Stimulation of Invariant NKT Cells Expands a Unique Tissue-Resident Population of Precursors to Mature NK Cells Endowed with Oncolytic and Antimetastatic Properties.

Invariant NKT (iNKT) cells are innate-like T lymphocytes that recognize and respond to glycolipid Ags such as α-galactosylceramide (α-GalCer … ells, which also expressed high levels of proliferation and tissue retention markers but diminished sphingosine-1-phosphate receptor 1, a receptor that facilitates tissue trafficking. Accordingly, FTY720, a sphingosine-1-phosphate receptor 1 antagonist, failed to prevent pre-mNK cells' intrahepatic accumulation. We found iNKT cell-driven expansion of pre-mNK …

Stable Isotope Kinetic Study of ApoM (Apolipoprotein M).

OBJECTIVE: ApoM (apolipoprotein M) binds primarily to high-density lipoprotein before to be exchanged with apoB (apolipoprotein B)-containin … related compartments according to plasma triglycerides (r=0.86; P<0.001). The relationships between sphingosine-1-phosphate and apoM were confirmed in all compartments (r range, 0.55-0.89; P<0.05). ApoM fractional catabolic rates and production rates were 0.16±0.07 pool/d and 0.14±0.06 mg/kg per day in high-density lipoprotein and 0.56±0.10 pool/d and 0.03±0. …

Dysregulation of sphingolipid and cholesterol homeostasis imposes oxidative stress in human spermatozoa.

Infertility is a significant public health concern, affecting one in six couples globally, with male-factor infertility representing half of … cations in human spermatozoa remains poorly understood. Sphingolipids, including Ceramide (Cer) and sphingosine-1-phosphate (S1P), are critical regulators of cellular functions that play a significant role in male reproductive health. These bioactive lipids and cholesterol promote sperm capacitation, motility, and the acrosome reaction (AR). We hypothesize th …

Hydrogen sulfide alleviates ischemia induced liver injury by repressing the SPHK1/S1P pathway.

BACKGROUND: Ischemia/reperfusion (I/R) induced liver injury is a severe pathological process which frequently occurs during clinical hepatic … yl-tetrazolium (MTT) assay and Hoechst analysis. The expression of C/EBP homologous protein (CHOP), sphingosine kinase 1 (SPHK1), and sphingosine 1-phosphate (S1P) were determined in hypoxic BRL-3A cells with or without H2S treatment. CHOP was overexpressed in hypoxic BRL-3A cells to further evaluate whether H2S protected the liver against I/R injury by decre …

Siponimod exerts neuroprotective effects on the retina and higher visual pathway through neuronal S1PR1 in experimental glaucoma.

Sphingosine-1-phosphate receptor (S1PR) signaling regulates diverse pathophysiological processes in the central nervous system. The role of S1PR signaling in neurodegenerative conditions is still largely unidentified. Siponimod is a specific modulator of S1P1 and S1P5 receptors, an immunosuppressant drug for managing secondary progressive multiple sclerosis. We investigated its neuroprotective properties in vivo on the retina and the brain in an optic nerve injury model induced by a chronic increase in intraocular pressure or acute N-methyl-D-aspartate excitotoxicity. Neuronal-specific deletio…

Case report: Variant-specific pre-exposure prophylaxis of SARS-CoV-2 infection in multiple sclerosis patients lacking vaccination responses.

Sphingosine-1-phosphate receptor modulators and anti-CD20 treatment are widely used disease-modifying treatments for multiple sclerosis. Unfortunately, they may impair the patient's ability to mount sufficient humoral and T-cellular responses to vaccination, which is of special relevance in the context of the SARS-CoV-2 pandemic. We present here a case series of six multiple sclerosis patients on treatment with sphingosine-1-phosphate receptor modulators who failed to develop SARS-CoV-2-specific antibodies and T-cells after three doses of vaccination. Due to their ongoing immunotherapy, lackin…

Autophagy augmentation alleviates cigarette smoke-induced CFTR-dysfunction, ceramide-accumulation and COPD-emphysema pathogenesis.

In this study, we aimed to investigate precise mechanism(s) of sphingolipid-imbalance and resulting ceramide-accumulation in COPD-emphysema. Where, human and murine emphysema lung tissues or human bronchial epithelial cells (Beas2b) were used for experimental analysis. We found that lungs of smokers and COPD-subjects with increasing emphysema severity demonstrate sphingolipid-imbalance, resulting in significant ceramide-accumulation and increased ceramide/sphingosine ratio, as compared to non-emphysema/non-smoker controls. Next, we found a substantial increase in emphysema chronicity-related c…

Diagnosis of lysosomal storage disorders: Gaucher disease.

Gaucher Disease (GD) is a progressive lysosomal storage disorder caused by deficiency of glucocerebrosidase (GBA). The clinical phenotype fo … bation of dried blood spots with the GBA-specific substrate D-glucosyl-β1-1'-N-dodecanoyl-D-erythro-sphingosine [C12-glucocerebroside (C36H69NO8)] and internal standard N-myristoyl-D-erythro-sphingosine [C14-ceramide (C32H63NO3)]. GBA activities in more than 2,000 newborn infants showed a mean of 22.0 ± 13.8 μmol/hr/liter (median: 19.9 μmol/hr/liter; 95% CI: …

Sphinganine-1-phosphate attenuates both hepatic and renal injury induced by hepatic ischemia and reperfusion in mice.

Hepatic ischemia/reperfusion (I/R) injury is a major complication after liver transplantation, major hepatic resection, or prolonged portal … ganine-1-phosphate-mediated hepatic and renal protection was blocked by VPC23019, an antagonist for sphingosine-1-phosphate type 1 receptor. Therefore, sphinganine-1-phosphate improves acute liver and kidney injuries after hepatic I/R via sphingosine-1-phosphate type 1 receptor-mediated inhibition of necrosis and apoptosis and by improving vascular integrity. …

Cell cycle arrest in Batten disease lymphoblast cells.

Batten disease is an inherited neurodegenerative disorder caused by a CLN3 gene mutation. Batten disease is characterized by blindness, seiz … ase patients. We found G1/G0 cell cycle arrest in Batten disease cells, with overexpression of p21, sphingosine, glucosylceramide, and sulfatide as possible cell cycle regulators.

Mechanistic perspective on the relationship between pyridoxal 5'-phosphate and inflammation.

A variety of inflammatory disease conditions have been found to be associated with low levels of plasma pyridoxal 5'-phosphate (PLP), the ac … e pathway of tryptophan degradation, metabolism of the immunomodulatory sphingolipids, ceramide and sphingosine 1-phosphate, and for serine hydroxymethylase for immune cell proliferation.

Etrasimod in Treatment of Ulcerative Colitis: A Comprehensive Review.

Ulcerative colitis (UC) is a chronic, inflammatory disease of the colon. The unpredictable, systemic, and debilitating nature of UC puts dis … herapeutic options in UC, with further detailing the molecular and clinical aspects of Etrasimod, a sphingosine-1-phosphate receptor (S1PR) modulator.

Потенциальные возможности FTY720: Новые терапевтические функции, цели и механизмы борьбы с заболеваниями.

Fingolimod (FTY720), антагонизатор фингозина-1-фосфата (S1P), функции привязки к рецепторам S1P (S1PRs), исключая S1PR2. В 2010 году Управление по контролю за продуктами питания и лекарственными препаратами (АПП) одобрило лечение множественных склерозов (МС). Как первый неселективный пероральный агонист для S1PR, разнообразное и системное выражение рецептора FTY720 часто приводит к изменениям в различных сигнальных путях и многосистемных системах, что делает его предметом интенсивных исследований. В ходе недавних исследований был выявлен широкий круг новых или потенциальных функций для FTY720,

Совпадение в аннотации оригинала
Fingolimod (FTY720), an antagonist of sphingosine-1-phosphate (S1P), functions by binding to S1P receptors (S1PRs), excluding S1PR2. It received approval from the Food and Drug Administration (FDA) for the treatment of multiple sclerosis (MS) in 2010. As the first non-selective oral agonist for S1PRs, FTY720's diverse and systemic receptor expression often l…