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GFAP and NfL as predictors of disease progression and relapse activity in fingolimod-treated multiple sclerosis.

In multiple sclerosis (MS) patients under therapy, the increase of serum glial fibrillary acidic protein (sGFAP) concentrations is associate … re not observed with other types of DMT and may hint to a specific anti-neurodegenerative effect of Sphingosine-1-phosphate-receptor modulators on astrocytes.

Effect of a high dose atorvastatin as adjuvant therapy to mesalamine in attenuating inflammation and symptoms in patients with ulcerative colitis: a randomized controlled pilot study.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon. Several preclinical studies investigated the beneficial effects of atorvastatin in colitis. Activation of sphingosine 1 phosphate (S1P)/ tumor necrosis factor-alpha (TNF-α)/ interleukin-6 (IL-6) pathways has been confirmed in the pathogenesis of UC and preclinical studies proved the efficacy of atorvastatin on these pathways. AIM: To investigate the role of atorvastatin on S1P/TNF-α/IL-6 pathway in UC. METHODS: Patients with mild to moderate UC were allocated into two groups in this pilot study. For 6 months…

Endothelial SRSF1 Promotes Ischemia-Induced Angiogenesis via ATF3-KLF2-S1PR1 Pathway.

BACKGROUND: Peripheral artery disease is a severe ischemic vascular pathology without effective pharmacological approaches and improving ang … ctly to the KLF2 (Krüppel-like factor 2) promoter, suppressed KLF2 expression and downstream S1PR1 (sphingosine-1-phosphate receptor 1) signaling. Through upregulation of full-length ATF3 and downregulating KLF2-S1PR1 signaling, SRSF1 promoted endothelial tube formation and angiogenesis. In addition, alprostadil, the prostaglandin E1 analog, could activate th …

Efficacy and safety of etrasimod in alopecia areata: A multicentre, randomized, double-blind, placebo-controlled, Phase 2 study.

BACKGROUND: Etrasimod, an oral, selective sphingosine 1-phosphate 1, 4 and 5 receptor modulator approved for the treatment of ulcerative colitis, has been studied in immune-mediated inflammatory diseases, including alopecia areata (AA). OBJECTIVES: To evaluate the efficacy and safety of etrasimod in adults with moderate to severe AA. METHODS: This Phase 2, randomized, double-blind, placebo-controlled trial included patients (aged ≥18 years) with moderate to severe AA, defined as a Severity of Alopecia Tool (SALT) score of ≥25. Patients were sequentially enrolled into two cohorts. Cohort 1 in…

Sex-Related Gap in the Use of Disease-Modifying Therapies in Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: In women with multiple sclerosis (MS), the therapeutic strategy may be influenced by the anticipation of future p … and 1 year for HEDMTs, and did not differ significantly according to patient's age. Teriflunomide, sphingosine-1-phosphate receptor modulators, and anti-CD20s were significantly underused in women throughout their entire period of availability; interferons β (IFN-β) and natalizumab were initially less used and then equally after some time; glatiramer acetate …

Longitudinal quantification of serum SARS-CoV-2 neutralising antibodies, pro-inflammatory cytokines, NfL and GFAP before and after breakthrough COVID-19 infection in CNS neuroimmunological diseases: a prospective observational study.

BACKGROUND: Immunosuppressive treatment can attenuate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced immune re … NMOSD. All had received at least three doses of the SARS-CoV-2 mRNA vaccine. Patients on anti-CD20/sphingosine-1-phosphate-receptor modulators (S1PRM) showed significantly reduced NAbs levels in both post-V4 and post-COVID-19 infection scenarios, compared to patients on other immunotherapies. No significant differences between baseline and post-COVID-19 infe …

Single-Cell Meta-Analysis Uncovers the Pancreatic Endothelial Cell Transcriptomic Signature and Reveals a Key Role for NKX2-3 in PLVAP Expression.

BACKGROUND: The pancreatic vasculature displays tissue-specific physiological and functional adaptations that support rapid insulin response … r function (PLVAP, EHD4, CAVIN3, HSPG2, ROBO4, HEG1, and CLEC14A), and key signaling pathways (S1P [sphingosine-1-phosphate], TGF-β [transforming growth factor-β], RHO/RAC GTPase [guanosine triphosphatase], PI3K/AKT [phosphoinositide 3-kinase/protein kinase B], and PDGF [platelet-derived growth factor]). The integrated atlas revealed the vascular hierarchy wi …

Effect of Siponimod on Brain and Spinal Cord Imaging Markers of Neurodegeneration in the Theiler's Murine Encephalomyelitis Virus Model of Demyelination.

Siponimod (Sp) is a Sphingosine 1-phosphate (S1P) receptor modulator, and it suppresses S1P- mediated autoimmune lymphocyte transport and inflammation. Theiler's murine encephalomyelitis virus (TMEV) infection mouse model of multiple sclerosis (MS) exhibits inflammation-driven acute and chronic phases, spinal cord lesions, brain and spinal cord atrophy, and white matter injury. The objective of the study was to investigate whether Sp treatment could attenuate inflammation-induced pathology in the TMEV model by inhibiting microglial activation and preventing the atrophy of central nervous tissu…

Characterization of Endophytic Fungi, Acremonium sp., from Lilium davidii and Analysis of Its Antifungal and Plant Growth-Promoting Effects.

The present study was aimed at isolating endophytic fungi from the Asian culinary and medicinal plant Lilium davidii and analyzing its antif … -pyrrolidine-2-carboxamido)propanoic acid, dibutyl phthalate (DBP), 9-octadecenamide, D-erythro-C18-Sphingosine, N-palmitoyl sphinganine, and hydroxypalmitoyl sphinganine. The strain Ld-03 showed indole acetic acid (IAA) production with or without the application of exogenous tryptophan. The IAA ranged from 53.12 ± 3.20 μg ml-1 to 167.71 ± 7.12 μg ml-1 under …

Sex Differences in the Immune System Become Evident in the Perinatal Period in the Four Core Genotypes Mouse.

We have used the four core genotypes (FCG) mouse model, which allows a distinction between effects of gonadal secretions and chromosomal com … cells. For CD8+ cells, male cells in the thymus were also found to express one third the density of sphingosine-1-phosphate thymic egress receptors per cell compared to female, a male characteristic most likely an indirect result of Sry expression. Interestingly, the data also support a previously unrecognized role for non-gonadal estradiol in the promotion o …

Diagnosis and Treatment of Multiple Sclerosis: A Review.

IMPORTANCE: Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease of the central nervous system characterized by infla … ongoing inflammatory activity. These drugs include interferons, glatiramer acetate, teriflunomide, sphingosine 1-phosphate receptor modulators, fumarates, cladribine, and 3 types of monoclonal antibodies. One additional DMT, ocrelizumab, is approved for primary progressive MS. These DMTs reduce clinical relapses and MRI lesions (new T2 lesions, gadolinium-en …

Ulcerative colitis: from molecular pathophysiology to management and the emerging role of natural and pharmacological drug candidates.

Ulcerative colitis (UC) is a chronic, relapsing, immune-mediated inflammatory disease of the colonic mucosa that imposes a substantial and g … , integrins, and the IL-12/23 axis, as well as small molecule modulators such as JAK inhibitors and sphingosine-1-phosphate receptor agonists-a substantial proportion of patients either fail to achieve remission or experience loss of response over time, underscoring the continued need for novel therapeutic approaches. This comprehensive review systematically …

Causal relationship between plasma metabolites and chronic regional pain: a Mendelian randomization study.

BACKGROUND: Chronic pain imposes an enormous economic and personal health burden worldwide, with more than one-third of the population affec … R analysis indicated that neck and shoulder pain was associated with a decreased AMP-to-N-palmitoyl-sphingosine ratio. CONCLUSIONS: This exploratory, hypothesis-generating MR study identifies candidate plasma metabolites and metabolic pathways potentially involved in chronic pain susceptibility across multiple anatomical sites. These findings provide a found …

Xiegan Liangxue Jiedu Decoction ameliorates psychiatric comorbidities in psoriasis via regulation of sphingolipid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiegan-Liangxue-Jiedu decoction (XLJD) is an ethnopharmacological empirical prescription inherited from Gu's … metabolism and ameliorated abnormal sphingolipid (SP) metabolism. It inhibited lesions mediated by sphingosine-1-phosphate signaling in lesioned skin. In the hippocampus, XLJD reduced the proportion of M1 microglia and exerted potential neuroprotective effects by inhibiting ASM expression and activity. CONCLUSIONS: Based on the TCM theory of Liver governing …

APOM-associated inflammation and apoptosis in stroke-exacerbated myocardial infarction: implications for brain-heart interactions.

Brain-heart syndrome (BHS) describes cardiac dysfunction secondary to central nervous system injury, with acute ischemic stroke (AIS) servin … ytokine release from cardiomyocytes. Concurrently, APOM deficiency led to a significant decrease in sphingosine-1-phosphate (S1P) and also caused myocardial lipid droplet accumulation and metabolite changes. Additionally, the loss of APOM increased the expression of D-dimer and fibrinogen family proteins. Our findings suggest that APOM is a potential cardiopr …

SEW2871 Attenuates Blood-Brain Barrier Damage and Neuropathological Outcomes Related to Cerebral Small Vessel Disease.

BACKGROUND: Blood-brain barrier (BBB) dysfunction contributes to the pathogenesis of cerebral small vessel disease. This study assessed SEW2871, a selective agonist of sphingosine-1-phosphate receptor 1, as a potential novel therapy for small vessel disease by targeting BBB damage using a rat model of small vessel disease. METHODS: Twelve-week male and female spontaneously hypertensive rat stroke-prones were subjected to unilateral carotid artery occlusion (UCAO) and Japanese permissive diet (JPD). Three doses of SEW2871 (0.5, 1.0, and 5.0 mg/kg, delivered every other day up to 5 weeks) were …

Feasibility of salivary lipid screening for caries biomarkers in young adults.

BACKGROUND: To identify distinct lipid metabolic profiles that differentiate young adults with dental caries (DC) from their caries-free (CF … (2OH)), phosphatidic acid (PA)(21:0_24:1), PA (25:0_20:1), phosphatidylcholine (PC)(16:0_24:0), and sphingosine (SPH)(d18:0), showed significant differences in both DC1 (decayed, missing, and filled teeth (DMFT) = 4-6) and DC2 (DMFT > 6) groups compared with CF controls (P < 0.001). Cer (d24:1/18:0(2OH)), PA (25:0_20:1), PA (21:0_24:1), and PC (16:0_24:0) wer …

Rutin Attenuates Oxidative Stress Responses and Hepatocyte Metabolomics in β-Hydroxybutyric Acid-Induced Hepatocyte Injury in Calves.

: Negative energy balance (NEB) in dairy cows induces excessive lipolysis, leading to elevated levels of β-hydroxybutyric acid (BHBA), which … ted 47 metabolites-including 8-hydroxy-2'-deoxyguanosine, 3-hydroxyisovaleric acid, and N-palmitoyl-sphingosine-and downregulated 58 metabolites, such as betaine, linolenic acid, and arachidonic acid. In contrast, RT pretreatment upregulated 207 metabolites relative to the BHBA treatment, including linolenic acid, taurocholic acid, and 4-hydroxybenzoic acid, …

An untargeted metabolomics analysis in feces and brain of Orthoflaviviruses-infected mice.

Annually, millions of people are affected by mosquito-borne Orthoflavivirus infections. These include diseases caused by the Dengue virus (D … metabolism is highly correlated with the biological function of the Orthoflavivirus envelope, where Sphingosine 1-phosphate (S1P) may be the key for Orthoflaviviruses to enter the human central nervous system via the GBA. This research is the first to explore the potential role of GBA in Orthoflavivirus infection through joint metabolomic analysis of fecal an …

Субрегиональная атрофия мозга в релапирующих и излучающих множественных склерозах: фазовая динамика и фармакологическая модуляция.

Атрофия головного мозга все чаще признается в качестве важной патологической особенности множественного склероза (MS). Вместе с тем конкретные модели на различных этапах и их изменение с помощью методов коррекции заболеваний (ДМТ) не вполне понятны. ЦЕЛЬ: Данное исследование было направлено на изучение в зависимости от стадии церебрального субрегионального изменения объема выбросов MS (RRMS) и оценку воздействия различных классов DMT на атрофию мозжечного мозга и клинические результаты. В ходе этого исследования было принято на работу 181 пациент, имеющий RRMS, и 99 здоровых больных. Пациенты

Совпадение в аннотации оригинала
BACKGROUND: Cerebellar atrophy is increasingly recognized as an important pathological feature of multiple sclerosis (MS). However, the spec … e, chronic-active, and chronic-inactive subgroups, and by pharmacological mechanism into untreated, sphingosine-1-phosphate (S1P)_T (siponimod, fingolimod, and ozanimod) and not_S1P_DMT (dimethyl fumarate and teriflunomide). Cerebellar subregional volumes were quantified using the deep learning-based tool, CerebNet. Group comparisons were conducted, and inter …