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Endothelial glycocalyx in perioperative medicine current understanding and future direction.

The endothelial glycocalyx (EG) is a dynamic, gel-like layer that lines the luminal surface of blood vessels, playing a crucial role in vasc … herapeutic strategies for preserving glycocalyx integrity include albumin, fresh frozen plasma, and sphingosine-1-phosphate, which stabilize endothelial junctions. Maintaining normovolemia during surgery is crucial, as both excessive fluid and hypovolemia can accelerate glycocalyx breakdown. Overall, the endothelial glycocalyx should be considered in perioper …

Emerging therapeutic pipelines on kidney fibrosis: challenges in translational research.

BACKGROUND: Chronic kidney disease (CKD) is estimated that by 2040, it will be the 5th highest cause of years of life lost globally due to t … relaxin) modulators of the WNT/β-catenin pathway; inhibitors of TGF-β (BMP-7, ncRNA, fresolimumab); sphingosine analogs (fingolimod). In addition to these indirect approaches, therapies with direct antifibrotic activity have also gained significant attention in the field. Among these alternatives, SGLT2 inhibitors and finerenone have emerged as particularly p …

Tracking COVID-19 Severity and Progression Through Amines and Lipid Mediators.

Coronavirus disease 2019 (COVID-19) exhibits a broad spectrum of severity, ranging from mild to critical cases. To reduce mortality and cost … erturbations in the tryptophan-kynurenine pathway, linoleic acid derivatives, endocannabinoids, and sphingosines were significantly associated with disease severity and progression. These metabolic changes correlated with immune markers reflecting COVID-19 severity. Some observed potential differences between the two waves could be partially attributed to the …

Fingolimod induces cytotoxic stress and apoptosis-like cell death in drug-sensitive and P-glycoprotein-overexpressing acute myeloid leukemia cells.

Over the last several years, sphingolipids have been shown to regulate numerous cellular processes, including cell adhesion, migration, proliferation, senescence, death, or differentiation. Dysregulation of sphingolipid metabolism or sphingolipid mediated signaling is usually found in malignant cells, supporting uncontrolled tumor growth, suppression of immune responses, or drug resistance of cancer cells. Hence, novel drugs targeting sphingolipid metabolism or signaling are investigated as promising anticancer agents. Fingolimod is a synthetic analogue of sphingosine and employed for the trea…

Bioinformatics exploration of the S1PR1 receptor in various human cancers and its clinical relevance.

BACKGROUND AND OBJECTIVE: S1PR1 (sphingosine-1-phosphate receptor 1) plays a critical role in key cancer-related processes such as cell migration, proliferation, and survival. While its functions are well-established in the cardiovascular and immune systems, its mechanism in cancer remains unclear. Our study aims to investigate the expression, mutations, post-translational modifications, and immune infiltration of S1PR1 across different cancers, and particularly focus on its potential as a therapeutic target and prognostic biomarker. METHODS: We utilized HPA, GTEx, TCGA and CPTAC bioinformati…

Effectiveness of etrasimod on disease activity and patient-reported outcomes in ulcerative colitis-EFFECT-UC: a non-interventional, multinational, prospective cohort study protocol.

INTRODUCTION: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). While etrasimod demonstrated efficacy in randomised controlled trials, understanding its effectiveness in an observational setting is crucial. METHODS AND ANALYSIS: EFFECT-UC is a prospective, multinational, non-interventional study to evaluate the real-world effectiveness of etrasimod in adults with moderately to severely active UC. The study consists of a 52-week treatment period and a 28-day safety follow-up pe…

Chemoenzymatic Synthesis of Glycosphingolipids Having an HNK-1 Epitope for Erythrocyte Cell Surface Remodeling.

Several neuropathies, such as Guillain-Barré syndrome and myelin-associated glycoprotein neuropathy (MAG), are caused by antibodies targetin … onversion of the thioglycosides into anomeric fluorides made it possible to enzymatically introduce sphingosine. The resulting compounds were acylated to provide 3-sulfo-glucuronyl- and glucuronyl-containing glycosphingolipids, respectively. The glycosphingolipids were employed to remodel the surface of erythrocytes to examine complement-mediated toxicity by …

N-acetylcysteine influence on PI3K/Akt/mTOR and sphingolipid pathways in rats with MASLD induced by HFD: a promising new therapeutic purpose.

Sphingolipid and glucose metabolism play important roles in the induction and progression of severe liver disorders like metabolic dysfuncti … athway proteins. NAC decreased dihydroceramide and ceramide levels and increased phosphorylation of sphingosine and sphinganine. This antioxidant also enhanced phosphorylated Akt, GSK3α/β, and P70 S6 kinase and decreased phosphorylated S6RP. In silico docking analysis of insulin signaling molecules evidenced the higher binding affinity of NAC with all tested …

Trends in utilization of advanced therapies in patients with inflammatory bowel diseases in the USA, 2021-2025.

BACKGROUND AND AIMS: Seven new advanced therapies, belonging to three new classes, have been approved for the treatment of inflammatory bowe … osis factor (TNF) antagonists (34.5%; P = .003), and stable use of vedolizumab (33.6%; P = .17) and sphingosine-1 phosphate receptor modulators (1.6%; P = .28). In 15 951 patients with Crohn's disease treated with advanced therapies, we observed an increase in use of IL23p19 antagonists (15.0% in Q1/2025; P = .003) and upadacitinib (5.9%; P < .001) and declin …

Small-molecule therapies for pediatric inflammatory bowel disease: toward precision medicine.

BACKGROUND: Pediatric inflammatory bowel disease (pIBD) often begins early in life, progresses rapidly, and is associated with impaired grow … bMed and clinical trial registries. Special emphasis is placed on Janus kinase (JAK) inhibitors and sphingosine-1-phosphate (S1P) modulators, which represent the main translational research focus in pediatric IBD. RESULTS: JAK inhibitors such as tofacitinib and upadacitinib have demonstrated promising efficacy in pediatric patients with refractory disease, a …

Possible Involvement of Lysophospholipids in Severe Asthma as Novel Lipid Mediators.

In severe asthma, symptoms are unstable despite intensive treatment based on high doses of inhaled corticosteroids and on-demand use of oral … ium, and epithelium in the airways. Lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC), and sphingosine 1-phosphate (S1P) are increased in bronchoalveolar fluid after allergen challenge. LPA, LPC, and S1P recruit eosinophils to the lungs and cause β2-adrenergic desensitization. LAP and S1P cause contraction and hyperresponsiveness in airway smooth mus …

Metabolism of sphingolipids in a rat spinal cord stenosis model.

BACKGROUND: Lumbar spinal canal stenosis (LSCS) plays a crucial role in neurogenic claudication and neuropathic pain. Recent studies suggest … inal cord significantly increased on day 28, and there was an increase in mRNA expression levels of sphingosine kinases (SphK)1 on days 1,7, and 28, while SphK2 on days 7 and 28. Regarding S1P receptors, there was an increase in mRNA expression levels of S1P1 on days 1,7, and 28 and S1P3 on day1. CONCLUSION: The production and activation of the sphingolipid …

[Treatment of severe flares in Crohn's disease and ulcerative colitis].

BACKGROUND: In chronic inflammatory bowel diseases (IBD), severe flares are characterized by intense inflammatory activity and a high diseas … (TNF)-α, α4ß7 integrins, interleukin (IL)-12/23 or IL-23, as well as Janus kinase (JAK) inhibitors, sphingosine 1‑phosphate receptor (S1PR) modulators, and calcineurin inhibitors, are available today, but there is no clear algorithm preferring one drug for CD or UC. Instead, treatment should be selected based on approvals, the patient's medical history, prior …

Impaired docking and recycling of synaptic vesicles in inherited lysosomal sphingolipidoses.

Cognitive, memory, and learning impairments are common features of many lysosomal sphingolipidoses, yet the underlying synaptic mechanisms r … tive analysis of other disease-associated sphingolipids-including gangliosides, sulfatides, glucosylsphingosine, globotriaosylceramide, sphingomyelin, and sphingosine-revealed distinct effects on vesicle trafficking, underscoring convergent yet lipid-specific mechanisms across inherited sphingolipidoses. Collectively, these findings identify presynaptic sphin …

When ganglioside pathways go awry: congenital disorders and experimental insights.

Glycosphingolipids comprise a hydrophobic ceramide backbone, consisting of a long-chain base (sphingosine) and a fatty acid, conjugated with a hydrophilic oligosaccharide moiety. These amphipathic molecules are integral constituents of cellular membranes, playing pivotal roles in modulating membrane protein functionality and receptor-mediated signaling. Among glycosphingolipids, gangliosides, defined by their inclusion of sialic acid residues, are abundantly enriched in the central nervous system. Notably, four predominant species, GM1, GD1a, GD1b, and GT1b, constitute the majority of ganglios…

Регулирование терапий, направленных на изменение болезней в множестве склероза и коморбидного ревматоидного артрита.

КОЛИЧЕСТВО: Комфортные аутоиммунные расстройства, включая ревматоидный артрит (RA), широко распространены среди людей с множественным склерозом (MS). Оба условия характеризуются патогенными сходствами, что создает возможность возможного дублирования в лечении. Несмотря на то, что многие методы лечения заболеваний (ДМТ) утверждаются для НР, а новые варианты подвергаются клиническим испытаниям, их эффективность в РЗ варьируется. Основные цели: Был проведен обзор литературы в Пубмеде для оценки воздействия утвержденных и в настоящее время расследуемых МЗ-ДМТ на МЗ и РЗ и наоборот. Некоторые MS-DM

Совпадение в аннотации оригинала
BACKGROUND: Comorbid autoimmune disorders, including rheumatoid arthritis (RA), are common in people with multiple sclerosis (MS). Both cond … ignificant impact (type-I interferons, Bruton´s tyrosine kinase (BTK) inhibitors) or lacked trials (sphingosine-1-phosphate receptor modulators, glatiramer acetate). In contrast, BTK inhibitors were shown to be effective for inactive secondary progressive forms of MS, whereas secukinumab showed limited effects in relapsing MS. Concerning DMT for RA in MS, no …

Обширная профайлировка T-Cell SARS-CoV-2 mRNA Вакцинация у пациентов с множественным склерозом, прошедших лечение с помощью DMT.

Согласно имеющимся данным, корректирующая болезнь терапия оказывает воздействие на клеточную и юморальную иммунную реакцию у лиц с множестве … демонстрируют индукцию широкой и отдельной реакции CD4+T-клеток в PwMS даже на anti-CD20 лечение и sphingosine-1-phosphate Модификация рецептора после SARS-CoV-2 Прививка от MRNA. Это было особенно заметно в CD4+высоком и CD4+CD154+T клетках. Наши результаты не поддерживают введение иммунной реакции CD8+T-клеток. В то время как в ходе лечения ослелизумаба и …

Promises of Lipid-Based Nanocarriers for Delivery of Dimethyl Fumarate to Multiple Sclerosis Brain.

Multiple sclerosis (MS) is a neurodegenerative autoimmune disorder of the central nervous system (CNS) infecting 2.5 million people worldwid … le variables can also significantly increase the risk of developing MS. Dimethyl fumarate (DMF) and sphingosine-1-phosphate (S1P) receptor modulators that may pass the blood-brain barrier and have positive direct effects in the CNS with quite diverse mechanisms of action raise the possibility that a combination therapy could be successful in treating MS. Lipi …

Imaging and molecular features of adenomyosis after menopause.

OBJECTIVES: To explore the imaging features and the molecular characterization of adenomyosis after menopause. STUDY DESIGN: An observation … genes implicated in the epithelial-mesenchymal transition, inflammation and fibrosis, including the sphingosine-1-phosphate (S1P) pathway, was evaluated and compared to matched non-menopausal adenomyosis specimens. MAIN OUTCOME MEASURES: Direct and indirect US features of adenomyosis according to Morphological Uterus Sonographic Assessment at TVUS. Molecular …

Characterisation and Clinical Relevance of Tertiary Lymphoid Structures in Primary Biliary Cholangitis.

BACKGROUND AND AIMS: The pathological characteristics of lymphocyte infiltration in the hepatic portal tracts of patients with primary bilia … cells. Bulk RNA sequencing of liver was performed in PBC patients with different TLS maturity. The sphingosine-1-phosphate receptor (S1PRs) modulator FTY720 was administered to dnTGFβRII mice to assess the role of TLSs on cholangitis. RESULTS: TLSs presented in 61.3% (46/75) of liver tissues from patients with PBC, including 26 patients with mature TLS (mTL …