Результаты поиска

Dimethyl fumarate ameliorates autoimmune hepatitis in mice by blocking NLRP3 inflammasome activation.

Dimethyl fumarate (DMF) is a fumaric acid derivative clinically approved for the treatment of some inflammatory diseases, but the underlying mechanism for its therapeutic effects remains incompletely understood. NLR family pyrin domain containing 3 (NLRP3) inflammasome activation has critical roles in innate immune responses to various infections and sterile inflammations. In this study, we aimed to explore whether DMF affects auto-immune hepatitis (AIH) in mice induced by concanavalin A (Con A) by modulating NLRP3 inflammasome activation. The results showed that DMF suppressed the activation …

Severe Relapses of Neuromyelitis Optica Spectrum Disorder During Treatment With Dimethyl Fumarate.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system, characterized by a specific antibody that selectively binds aquaporin-4 channel.This is a report of an NMOSD case, with severe attacks of optic neuritis and myelitis after initiate of dimethyl fumarate (DMF).We suggested that DMF could deteriorate the neuromyelitis optica (NMO) disease course, which results in serious morbidity and mortality in patients. Thus, initiation of DMF should be avoided before ruling out NMOSD in patients experiencing demyelinating attacks, especially i…

Novel Heme Oxygenase-1 (HO-1) Inducers Based on Dimethyl Fumarate Structure.

Novel heme oxygenase-1 (HO-1) inducers based on dimethyl fumarate (DMF) structure are reported in this paper. These compounds are obtained by modification of the DMF backbone. Particularly, maintaining the α, β-unsaturated dicarbonyl function as the central chain crucial for HO-1 induction, different substituted or unsubstituted phenyl rings are introduced by means of an ester or amide linkage. Symmetric and asymmetric derivatives are synthesized. All compounds are tested on a human hepatic stellate cell line LX-2 to assay their capacity for modifying HO-1 expression. Compounds 1b, 1l and 1m s…

Oral Dimethyl Fumarate in Children With Multiple Sclerosis: A Dual-Center Study.

BACKGROUND: First-line injectable therapies for multiple sclerosis in children may be ineffective or not well-tolerated. There is therefore an urgent need to explore oral medications for pediatric multiple sclerosis. We review our dual-center experience with oral dimethyl fumarate. METHODS: This study was a retrospective review of children 18 years of age or less with multiple sclerosis treated with dimethyl fumarate at Yale University and the University of Colorado. Clinical, demographic, and magnetic resonance imaging parameters were analyzed. RESULTS: We identified 13 children treated wit…

Dimethyl fumarate modulation of immune and antioxidant responses: application to HIV therapy.

The persistence of chronic immune activation and oxidative stress in human immunodeficiency virus (HIV)-infected, antiretroviral drug-treated individuals are major obstacles to fully preventing HIV disease progression. The immune modulator and antioxidant dimethyl fumarate (DMF) is effective in treating immune-mediated diseases and it also has potential applications to limiting HIV disease progression. Among the relevant effects of DMF and its active metabolite monomethyl fumarate (MMF) are induction of a Th1 to Th2 lymphocyte shift, inhibition of pro-inflammatory cytokine signaling, inhibitio…

Between-hospital variation in discontinuation of treatment with dimethyl fumarate in multiple sclerosis.

BACKGROUND: In multiple sclerosis (MS), switching disease modifying treatment is associated with higher relapse rate, healthcare expenses, disease burden, and lower quality of life. We compared drug discontinuation rates of dimethyl fumarate (DMF) between hospitals in Denmark and Norway. METHOD: Data from national MS registries were analyzed, adjusting for sex, age, disease duration, Expanded Disability Status Scale, and baseline relapses. Between-hospital variation was assessed using median hazard ratios (MHR). RESULTS: 3368 patients with relapsing-remitting MS started DMF at all clinics in…

Breaking the cycle: Reversal of flux in the tricarboxylic acid cycle by dimethyl fumarate.

OBJECTIVE: To infer molecular effectors of therapeutic effects and adverse events for dimethyl fumarate (DMF) in patients with relapsing-remitting MS (RRMS) using untargeted plasma metabolomics. METHODS: Plasma from 27 patients with RRMS was collected at baseline and 6 weeks after initiating DMF. Patients were separated into discovery (n = 15) and validation cohorts (n = 12). Ten healthy controls were also recruited. Metabolomic profiling using ultra-high-performance liquid chromatography mass spectrometry (UPLC-MS) was performed on the discovery cohort and healthy controls at Metabolon Inc (…

Therapeutic Targeting of TAZ and YAP by Dimethyl Fumarate in Systemic Sclerosis Fibrosis.

Systemic sclerosis (scleroderma, SSc) is a devastating fibrotic disease with few treatment options. Fumaric acid esters, including dimethyl fumarate (DMF, Tecfidera; Biogen, Cambridge, MA), have shown therapeutic effects in several disease models, prompting us to determine whether DMF is effective as a treatment for SSc dermal fibrosis. We found that DMF blocks the profibrotic effects of transforming growth factor-β (TGFβ) in SSc skin fibroblasts. Mechanistically, we found that DMF treatment reduced nuclear localization of transcriptional coactivator with PDZ binding motif (TAZ) and Yes-associ…

The real-world patient experience of fingolimod and dimethyl fumarate for multiple sclerosis.

BACKGROUND: Oral disease-modifying therapies offer equivalent or superior efficacy and greater convenience versus injectable options. OBJECTIVES: To compare patient-reported experiences of fingolimod and dimethyl fumarate. METHODS: Adult relapsing-remitting multiple sclerosis patients treated with fingolimod or dimethyl fumarate were recruited from an online patient community and completed an online survey about treatment side effects, discontinuation, and satisfaction. RESULTS: 281 patients in four groups completed the survey: currently receiving fingolimod (CF, N = 61), currently receivin…

Сравнительная эффективность Diroximel Fumarate vs. Диметил Фумарат у лиц с множественным склерозом: анализ претензий США в отношении релапсовых результатов.

ВВЕДЕНИЕ: Дирошимель фумарат (DRF) и диметилфумарат (DMF) представляют собой лекарственные средства для изменения заболеваний в связи с повторным склерозом (RMS). Несмотря на то, что ДРР продемонстрировал более высокую терпимость к желудочно-кишечному кишечнику по сравнению с ДМФ, в настоящее время проводятся ограниченные исследования для оценки того, приводит ли эта разница в терпимости к клинической эффективности. В этом исследовании была дана оценка реальной эффективности ДРР и ДМФ в сравнении с результатами рецидивов у лиц, имеющих МЗС (PwMS) у большого населения США. МЕТОДЫ: В этом ретрос

Совпадение в аннотации оригинала
INTRODUCTION: Diroximel fumarate (DRF) and dimethyl fumarate (DMF) are established disease-modifying therapies for relapsing multiple sclerosis (RMS). While DRF has demonstrated improved gastrointestinal tolerability compared to DMF, there is limited research evaluating whether this difference in tolerability translates into a difference in clinical effectiv…

Dimethyl Fumarate Attenuates Behavioral and Structural Impairments Associated with Brain Ischemia in Rats.

INTRODUCTION: Ischemic stroke remains one of the leading causes of death and physical and mental disability. Oxidative stress, free radicals, and inflammation play critical roles in ischemic brain damage. Free radical scavengers such as edaravone and dimethyl fumarate (DMF), known for their antioxidant and anti-inflammatory properties, are considered promising targets for ischemic stroke treatment. This study aimed to assess the impact of these drugs on brain ischemia. METHODS: Forty-nine rats were randomly divided into seven groups: sham, edaravone, and DMF controls, as well as edaravone, DM…

Dimethyl fumarate as a versatile therapeutic agent: molecular mechanisms and potential clinical applications.

Dimethyl fumarate (DMF) is an electrophilic compound used clinically for multiple sclerosis and psoriasis. We elaborate here that the pharmacological effects of DMF extend beyond the well-known activation of the NRF2 antioxidative pathway. Indeed, DMF directly modifies reactive cysteine residues on multiple proteins in immune and neural cells, leading to diverse anti-inflammatory, immunomodulatory, and neuroprotective actions. Recent studies revealed that DMF may affect proteins involved in inflammasome activation, glycolysis, and cell signaling pathways, including JAK-STAT and NF-kB. These ef…

Dimethyl fumarate improves sepsis-induced acute lung injury by inhibiting STING-mediated ferroptosis.

The precise pathogenic mechanisms underlying sepsis-induced acute respiratory distress syndrome (ARDS) remain incompletely characterized. Emerging evidence implicates ferroptosis of alveolar epithelial cells in ARDS pathogenesis, though the regulatory networks governing this association require further elucidation. Stimulator of interferon genes (STING), conventionally recognized as a pivotal mediator of innate immunity through DNA-sensing pathways, has recently been linked to ferroptosis. This investigation elucidates the pulmonary protective mechanisms of DMF in sepsis-induced ALI models. Ex

Drug repurposing of dimethyl fumarate in Parkinson's disease: a promising disease-modifying strategy.

UNLABELLED: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of nigrostriatal dopaminergic neurons and pathological aggregation of a-synuclein. Despite advancements in symptomatic treatment, there is a critical unmet need for disease-modifying therapies capable of halting or slowing disease progression. Drug repurposing offers an efficient, cost-effective strategy to identify new treatments by leveraging the established safety and pharmacokinetic profiles of existing compounds. Dimethyl fumarate (DMF), an FDA-approved drug for multiple sclerosis an…

Medication persistence among people with multiple sclerosis in Slovenia treated with dimethyl fumarate.

OBJECTIVE: Multiple sclerosis is a chronic, demyelinating inflammatory disease of the central nervous system. Medication persistence is defined as an interval between the initiation and last dose of the applied medication and presents a useful surrogate marker of a stable disease course. This observational study aimed to evaluate medication persistence and discontinuation reasons in Slovenian people with multiple sclerosis treated with dimethyl fumarate. METHODS: Our retrospective cohort study evaluated people with relapsing-remitting multiple sclerosis treated with dimethyl fumarate as an in…

Dimethyl Fumarate-Induced Takotsubo Cardiomyopathy in a Patient With Relapsing-Remitting Multiple Sclerosis.

Dimethyl fumarate (DMF) is an approved oral pharmacologic agent used in the treatment of relapsing-remitting multiple sclerosis (RRMS). Although commonly used in clinical practice, its mechanism of action remains largely unknown. Some frequent side effects associated with this drug are angioedema, hepatic injury, flushing, herpes zoster infection, and abdominal pain among others. A 47-year-old female presented with symptoms of an allergic reaction after initiating DMF therapy. She required intensive care unit admission due to an acute-hypoxic respiratory failure. A transthoracic echocardiogram…