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LDLR-OPN Interaction Drives COVID-19 Myocarditis Through Monocyte Recruitment.

COVID-19-associated myocarditis is marked by macrophage-rich inflammation and adverse cardiac outcomes, yet its mechanisms remain unclear. W … uitment. Induced degrader of LDLR-mediated LDLR degradation completely abrogated myocarditis, while dimethyl fumarate significantly reduced pyroptosis and inflammatory burden. Importantly, human myocarditis autopsy hearts exhibited >10-fold up-regulation of LDLR and intercellular adhesion molecule-1, mirroring the murine findings. These data establish the LDLR-oste …

Static and group-based trajectory analyses of factors associated with non-adherence in patients with multiple sclerosis newly-initiating once- or twice-daily oral disease-modifying therapy.

BackgroundIncreased understanding of adherence may facilitate optimal targeting of interventions.ObjectiveTo utilize group-based trajectory modeling (GBTM) to understand longitudinal patterns of adherence and factors associated with non-adherence in patients with multiple sclerosis (MS) newly-initiating once-/twice-daily oral disease-modifying therapy (DMT) (fingolimod, dimethyl fumarate, or teriflunomide).MethodsCommercial plan data were analyzed using proportion of days covered (PDC) to evaluate factors associated with non-adherence. GBTM clustered patient subgroups with similar longitudinal…

Understanding Progressive Multifocal Leukoencephalopathy Risk in Multiple Sclerosis Patients Treated with Immunomodulatory Therapies: A Bird's Eye View.

The increased use of newer potent immunomodulatory therapies for multiple sclerosis (MS), including natalizumab, fingolimod, and dimethyl fumarate, has expanded the patient population at risk for developing progressive multifocal leukoencephalopathy (PML). These MS therapies shift the profile of lymphocytes within the central nervous system (CNS) leading to increased anti-inflammatory subsets and decreased immunosurveillance. Similar to MS, PML is a demyelinating disease of the CNS, but it is caused by the JC virus. The manifestation of PML requires the presence of an active, genetically rearr…

Recent progress and applications of small molecule inhibitors of Keap1-Nrf2 axis for neurodegenerative diseases.

The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway serves as a crucial regulator against oxidative stress (OS) damage in various cells and organs. It has garnered significant attention as a potential therapeutic target for neurodegenerative diseases (NDD). Although progress has been achieved in strategies to regulate the Keap1-Nrf2 pathway, the availability of Nrf2 activators applicable to NDD is currently limited. Currently, the FDA has approved the Nrf2 activators dimethyl fumarate (DMF) and Omaveloxolone (Omav) as novel first-line oral…

Воздействие дироксимела фумарата на кишечную дисбиоз и автоиммунитет в центральной нервной системе.

Diroximel fumarate (DRF) — утвержденное лечение повторно излучаемого многократного склероза (RRMS). По сравнению с диметилфумаратом (ДМП) он продемонстрировал бо́льшую желудочно-кишечную пригодность. Недавние исследования показывают, что дисбиоз кишечника может способствовать развитию множественных склерозов (МС) и что сокращение кишечного дисбиоза может быть полезным для развития заболеваний. В этом исследовании изучалось воздействие ДРР на дисбиоз кишечника и нейроинфламмацию в экспериментальном аутоиммунном энцефаломиелите (EAE) — животной модели MS. Мы изучили влияние ДРР на выражение α4β1

Совпадение в аннотации оригинала
Diroximel fumarate (DRF) is an approved treatment for relapsing-remitting multiple sclerosis (RRMS). It has demonstrated better gastrointestinal tolerability compared to dimethyl fumarate (DMF). Recent studies indicate that gut dysbiosis may contribute to the development of multiple sclerosis (MS) and that reducing gut dysbiosis may be beneficial for disease…

Anesthetic management of a patient with multiple sclerosis undergoing cesarean section with low dose epidural bupivacaine.

A 32-year-old Indian female 38 weeks pregnant, with a history of multiple sclerosis since 2008 was admitted in obstetric ward for safe confinement. She had a history of diminution of vision in both eyes and limb weakness, relapsing - remitting type with movement-induced muscle spasms, in all the four limbs. Her symptoms were usually diplopia, difficulty in vision and ataxic gait. Sh was then treated with methylprednisolone. She was on oral dimethyl fumarate trial, which was stopped at the beginning of pregnancy. Presently, she was completely asymptomatic. Epidural anesthesia with an indwelling…

Pharmacological studies on nonimmunologic contact urticaria in guinea pigs.

In the present study we examined the effects of chlorpheniramine and ranitidine, indomethacin, BW755C (an inhibitor of cyclo-oxygenase and lipo-oxygenase enzymes of arachidonic acid metabolism), dexamethasone, and capsaicin on nonimmunologic contact urticaria (NICU) induced in the guinea pig ear by benzoic, acid cinnamic acid, cinnamic aldehyde, methyl nicotinate, diethyl fumarate, or dimethyl sulfoxide. The intensity of edema in the urticarial reaction was quantified by measuring the ear thickness. Antihistamines inhibited reactions to intradermal histamine but not to agents causing NICU. Ind

Metabolic characteristic changes in local tissues after high-intensity focused ultrasound treatment for uterine fibroids.

PURPOSE: To investigate the changes in the metabolome of fibroid tissue after high-intensity focused ultrasound (HIFU) treatment, providing … he treated fibroid tissue and the myometrial tissue in HIFU group. The levels of malus pumila acid, dimethyl fumarate, fumaric acid, methylphenylacetic acid, benzoic acid, and phosphoenolpyruvic acid were significantly higher (p < 0.05), and acetophenone, hexanoic acid, and idketoglutaric acid monoamide exhibited significantly decreased levels in the HIFU group (p …

Demyelinating disease (multiple sclerosis) in a patient with psoriatic arthritis treated with adalimumab: a case-based review.

Over the past two decades, tumor necrosis factor-α (TNF-α) inhibitors became one of the most important drugs in the treatment of patients wi … remitting type of multiple sclerosis and treated with oral and pulse glucocorticoids and later with dimethyl fumarate. Adalimumab was discontinued. The question remains was the demyelination induced by the TNF-α blockade or was it unmasked by the introduction of the cytokine blocking agent. In patients suffering from inflammatory arthritis, treating disease to targ …

Treatment of therapy-resistant Alopecia areata with fumaric acid esters.

BACKGROUND: Alopecia areata is a cosmetically very disfiguring clinical picture and can be a great emotional burden to the patient, especially when persisting for a longer period of time. PATIENTS AND METHODS: 10 patients with an alopecia resistant to therapy were treated within the bounds of an open, non-placebo controlled pilot study with fumaric acid esters (FAE's, Fumaderm) for a period of six months and a maximum dose of 120 mg dimethylfumarate per day. The shortest space of time between persistent Alopecia areata and the start of the therapy with FAE was between six months and 17 years.

In vivo Effects of Disease-modifying Therapies on Immunological Subsets in Patients with Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Disease-modifying therapies (DMTs) are aimed at controlling Multiple Sclerosis disease by modulating or suppressing the immune system. However, there is limited data on changes in immune cell subsets induced by these treatments. OBJECTIVE: To assess differences in myeloid, T-, and B-cell subsets in the peripheral blood of relapsing- remitting MS (RR-MS) patients treated with different DMTs. METHODS: This longitudinal study enrolled all RR-MS patients treated with cladribine (CLAD), dimethyl fumarate (DMF), and natalizumab (NTZ) between July 2022 and September 2022. All patients u…

Nrf2 activation rescues stress-induced depression-like behaviour and inflammatory responses in male but not female rats.

BACKGROUND: Major depressive disorder (MDD) is a recurring affective disorder that is two times more prevalent in females than males. Eviden … estigated the sex-specific antidepressant and immunomodulatory effects of the potent Nrf2 activator dimethyl fumarate (DMF), as well as the associated gene expression profiles. METHODS: Male and female rats were treated with vehicle or DMF (25 mg/kg) whilst subjected to 8 weeks of chronic unpredictable stress. The effect of DMF treatment on stress-induced depressi …

Pharmacological modulation of inflammatory oligodendrocyte progenitor cells using three multiple sclerosis disease modifying therapies in vitro.

Preclinical studies of pro-remyelinating therapies for multiple sclerosis tend to neglect the effect of the disease-relevant inflammatory milieu. Interferon-gamma (IFN-γ) is known to suppress oligodendrocyte progenitor cell (OPC) differentiation and induce a recently described immune OPC (iOPC) phenotype characterized by expression of major histocompatibility complex (MHC) molecules. We tested the effects of cladribine (CDB), dimethylfumarate (DMF), and interferon-beta (IFN-β), existing anti-inflammatory therapies for MS, on the IFN-γ-induced iOPC formation and OPC differentiation block. In li

To wait, or too late? Modeling the effects of delayed ofatumumab treatment in relapsing-remitting multiple sclerosis.

BACKGROUND: Several disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis (RRMS) reduce relapse rates and slow disease progression. RRMS DMTs have varying efficacy and administration routes; DMTs prescribed first may not be the most effective on relapses or disease progression. Here, we aimed to quantify the benefit of initiating ofatumumab, a high-efficacy DMT, earlier in the treatment pathway. METHODS: Aggregate data from a real-world cohort of patients with RRMS, who were eligible for dimethyl fumarate (DMF) or ofatumumab treatment within the UK National Health Ser…

Branched-Chain Amino Acids Exacerbate Colitis Progression by Lowering Colonic Fumarate Levels.

BACKGROUND: Ulcerative colitis (UC) is a gastrointestinal inflammatory condition with an unclear etiology. Recent findings suggest that meta … ng and metabolomic profiling of stool extracts were performed. Additionally, mice were treated with dimethyl fumarate (DMF) post-supplementation to explore therapeutic interventions. RESULTS: BCAA supplementation exacerbated colitis severity in mice, as evidenced by worsened DAI, increased histological damage, and significant alterations in immune cell populations …

Cost-effectiveness of cladribine tablets for the treatment of active relapsing-remitting multiple sclerosis in the United Kingdom.

OBJECTIVE: The approved indication of cladribine tablets has recently been expanded in the United Kingdom for the treatment of all adult pat … tablets were dominant (i.e. less costly and more effective) vs ponesimod, ocrelizumab, ofatumumab, dimethyl fumarate, diroximel fumarate, and teriflunomide in pairwise comparisons. Over a lifetime horizon, the model predicted discounted cost-savings with cladribine tablets vs high-efficacy comparators (ponesimod, ocrelizumab, and ofatumumab). In most scenarios, th …

State-Dependent 3D Enhancer Architecture Resolves a Shared Schizophrenia and Multiple Sclerosis Ketone and Lactate Sensing Logic Gate.

Recent cross-disorder meta-analyses have revealed substantial pleiotropic genetic architectures shared between Schizophrenia (SCZ) and Multi … while explaining the profound clinical efficacy of HCAR2 synthetic agonists, derived from the drug dimethyl fumarate (which forms the monomethyl fumarate metabolite), in halting demyelinating disease.

Cancer diagnosis in a Spanish cohort of multiple sclerosis patients under dimethylfumarate treatment.

BACKGROUND: Potential increase of cancer incidence is one of the main safety concerns of the disease-modifying therapies employed in Multiple Sclerosis (MS). OBJECTIVE: Detailed description of patients who developed cancer among a prospective cohort of Spanish MS patients on dimethyl fumarate (DMF) treatment. METHODS: We describe patients who developed cancer among a cohort of 886 MS patients on DMF treatment (2681 patient-years), with a median time of exposure of 39.5 months (IQR 23-51.5), who participated in a multicentre and prospective real-world study conducted in 16 Spanish National He…

Fumaric acid esters in necrobiosis lipoidica: results of a prospective noncontrolled study.

BACKGROUND: Necrobiosis lipoidica (NL) is an uncommon granulomatous skin disease with association to diabetes mellitus. To date, no proven effective therapy for NL has been implemented. The standard treatment is topical application of corticosteroids, but numerous agents have been reported for NL, with varying degrees of success. In recent case reports, fumaric acid esters (FAE) have been reported to be effective in granulomatous skin diseases such as granuloma annulare, cutaneous sarcoidosis and NL. OBJECTIVES: We sought to investigate the efficacy of FAE in a larger number of patients with