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Cost-Effectiveness Analysis of Ofatumumab for the Treatment of Relapsing-Remitting Multiple Sclerosis in Canada.

BackgroundOfatumumab is a high-efficacy disease-modifying therapy (DMT) approved for first-line treatment of relapsing-remitting multiple sc … es for RRMS, ofatumumab was dominant (more effective, lower costs) over teriflunomide, interferons, dimethyl fumarate, and ocrelizumab. Compared with glatiramer acetate and best supportive care, ofatumumab resulted in incremental cost-effectiveness ratios (ICERs) of $24,189 Canadian dollars per quality-adjusted life-year (QALY) and $28,014/QALY, respectively. At a …

Anaerostipes hominis sp. nov., a novel butyrate-producing bacteria isolated from faeces of a patient with Crohn's disease.

Cultivation and isolation of gut bacteria are necessary for understanding their role in the intestinal ecosystem. We isolated a novel bacterium, designated strain BG01T, from the faeces of a patient with Crohn's disease. Strain BG01T was a strictly anaerobic, rod-shaped, Gram-variable and endospore-forming bacterium. Strain BG01T possessed C12 : 0, C18 : 0 dimethyl aldehyde (DMA) and C18 : 1  ω9c DMA as predominant cellular fatty acids and meso-diaminopimelic acid as a diagnostic diamino acid. Strain BG01T grew at 15-45 °C (optimum, 37 °C), with 0-4 % (w/v) NaCl (optimum, 0-1 %), at pH 6-10 (o

Engineering human myelin microphysiological systems for testing patient treatment response in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by neuroinflammation, demyelination, and neurod … nonresponder profiles following treatment with prednisone, glatiramer acetate, interferon β-1a, or dimethyl fumarate. Thus, the myelin MPS platform provides a scalable, human pathophysiology-relevant platform for functional phenotyping and individualized treatment-response evaluation in MS.

Resveratrol Improves Cognitive Function in Post-stroke Depression Rats by Repressing Inflammatory Reactions and Oxidative Stress via the Nrf2/HO-1 Pathway.

Post-stroke depression (PSD) is a prevalent mental health issue, and resveratrol (RES) has been implicated in its management. This study aim … ed by co-treating rats with RES and either an Nrf2 pathway specific inhibitor (ML385) or activator (dimethyl fumarate). PSD rats exhibited depressive behaviors, disrupted neurotransmitter levels, and oxidative stress markers. RES treatment effectively alleviated these symptoms and activated the Nrf2/HO-1 pathway in PSD rat brain tissues. Co-administration of ML385 …

NLRP3 targets HMGB1 to exacerbate the pyroptosis of canine corneal epithelial cells infected with Staphylococcus pseudintermedius.

PURPOSE: This study focused on the mechanisms of pyroptosis and oxidative damage exacerbation by NOD-like receptor thermal protein domain associated protein 3 (NLRP3) during the infection of canine corneal epithelial cells (CCECs) with Staphylococcus pseudintermedius. METHODS: The CCECs treated with dimethyl fumarate (DMF), recombinant high mobility group protein 1 (HMGB1), or N-acetylcysteine (NAC). The gasdermin (GSDM) family and HMGB1 mRNA expression levels were detected using quantitative reverse transcription polymerase chain reaction. Lactate dehydrogenase activity, bacterial counts, th…

Exploring Psoriasis Inflammatory Microenvironment by NanoString Technologies.

Psoriasis is a chronic inflammatory skin disease whose molecular mechanisms and microenvironment are poorly understood. We performed gene expression analysis through the nCounter® PanCancer Immune Profiling Panel (NanoString Technologies, Seattle, WA, USA) on 22 FFPE punch biopsies from 19 psoriasis-affected patients. A subset of five cases was analyzed before (T0) and after 6 months (T6) of treatment with dimethyl fumarate (DMF) to address immune microenvironment changes. Molecular comparisons according to biopsy site and age of onset showed a different distribution of innate immune cells (ma…

Treatments of paediatric multiple sclerosis: Efficacy and tolerance in a longitudinal follow-up study.

AIM: To compare the efficacy and safety of newer and/or second-line disease-modifying treatments (DMTs) with interferon beta-1a. METHOD: This observational retrospective study included patients younger than 18 years old in the French KIDBIOSEP cohort who had a diagnosis of relapsing multiple sclerosis between 2008 and 2019 and received at least one DMT. Primary outcome was the annualized relapse rate (ARR). Secondary outcomes were the risk of new T2 or gadolinium-enhanced lesions on brain MRI. RESULTS: Among 78 patients enrolled, 50 were exposed to interferon and 76 to newer DMTs. Mean ARR w

Pregnancy and Family Planning in Multiple Sclerosis.

PURPOSE OF REVIEW: This article provides practical guidance on successful management of women with multiple sclerosis (MS) through pregnancy … ), known risk of severe rebound relapses (fingolimod, natalizumab), or unclear but plausible risks (dimethyl fumarate, alemtuzumab) to women of childbearing age who desire pregnancy or are not on reliable birth control. If a treatment needs to be resumed during breast-feeding, clinicians should opt for glatiramer acetate, interferon beta, natalizumab, or rituximab/ …

Heme oxygenase-1 deficiency accompanies neuropathogenesis of HIV-associated neurocognitive disorders.

Heme oxygenase-1 (HO-1) is an inducible, detoxifying enzyme that is critical for limiting oxidative stress, inflammation, and cellular injur … siRNA derepression or with nonselective pharmacologic inducers, including the CNS-penetrating drug dimethyl fumarate (DMF), decreased supernatant glutamate and neurotoxicity. Furthermore, IFN-γ, which is increased in CNS HIV infection, reduced HO-1 expression in cultured human astrocytes and macrophages. These findings indicate that HO-1 is a protective host facto …

A retrospective claims analysis: Compliance and discontinuation rates among Canadian patients with multiple sclerosis treated with disease-modifying therapies.

BACKGROUND: Compliance to disease modifying therapy (DMT) is associated with a reduced risk of relapse, lower healthcare resource utilization, and improved health-related quality of life in patients with multiple sclerosis (MS). Our objective was to assess the compliance and discontinuation rates of fingolimod relative to other oral, injectable, and infusible DMTs available on the market at the time of the study in Canada in patients with relapsing-remitting MS (RRMS). METHODS AND FINDINGS: We conducted a retrospective claims analysis. Patients with RRMS with ≥ 1 prescription for each DMT wer

Деэскалация терапии болезней в условиях множественного склероза - Датское общенациональное исследование кохарта.

ЦЕЛЬ И СПРАВОЧНАЯ ИНФОРМАЦИЯ: Для лечения множественных склерозов (МС) все шире используются высокоэффективные методы лечения (ДМТ) с модифицирующими заболеваниями. Озабоченность возникает при рассмотрении вопроса о снижении эффективности и повышении риска неблагоприятных последствий для пожилых пациентов. Мы пытались описать активность заболеваний и траектории лечения у пациентов с MS, которые деэскалировали от DMT HE до DMT с умеренной эффективностью (ME). МЕТОДЫ: Мы провели когортное исследование на основе данных Датского регистра множественных склерозов (ДМСР), включая пациентов с релапсир

Совпадение в аннотации оригинала
BACKGROUND AND OBJECTIVE: High-efficacy (HE) disease-modifying therapies (DMT) are increasingly used to treat multiple sclerosis (MS). Conce … asons. Most patients de-escalated from natalizumab or fingolimod (43.8% and 42.0%, respectively) to dimethyl fumarate (47.5%). At 2 years after de-escalation, the cumulative risk of relapse was 38% (95% CI 31-44) and 53% (95% CI 46-60) for inflammatory disease activity (relapses and/or radiological disease activity). Age (HR 0.96, 95% CI 0.94-0.98) and inflammatory …

Pharmaceutical therapies for pyroptosis in lung injury.

Pyroptosis, a form of programmed cell death characterized by inflammation, plays a significant role in the pathogenesis of lung injury. This … ays. Additionally, several synthetic small molecule drugs, including MCC950, disulfiram, VX765, and dimethyl fumarate, effectively intervene by binding to essential pyroptosis effector proteins. The use of NLCs enhances the in vivo bioavailability of these poorly soluble compounds and improves their targeted enrichment within damaged lung tissue. Furthermore, mesen …

Manifestations of tuberculosis possibly associated with rituximab in a patient with diagnosed multiple sclerosis: a case report.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system. Following the elucidation of the role of … rd anti-TB regimen (isoniazid, rifampin, pyrazinamide, and ethambutol). Rituximab was discontinued; dimethyl fumarate was introduced after four months of therapy and rituximab was reintroduced at six months. At one-year follow-up, there was no TB reactivation and no worsening of MS. CONCLUSION: This case demonstrates an atypical multisystem presentation of tubercu …

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 … ilizumab, sarilumab). Adverse events, including RA exacerbation, were reported for some MS-DMT like dimethyl fumarate, alemtuzumab, and natalizumab. Tumor necrosis factor alpha (TNFα) inhibitors increased disease activity in MS patients. CONCLUSION: Among approved DMT for MS and RA, teriflunomide and anti-CD20 therapies are the most suitable options for moderately …

Nrf2/FSP1/CoQ10 axis-mediated ferroptosis is involved in sodium aescinate-induced nephrotoxicity.

Sodium aescinate (SA), an active compound found in horse chestnut seeds, is widely used in clinical practice. Recently, the incidence of SA- … bp ARE site in FSP1 promoter, resulting in FSP1 suppression. Overexpression of Nrf2 or its agonist dimethyl fumarate (DMF) promoted FSP1 expression, thereby improving cellular antioxidant capacity and alleviating SA-induced ferroptosis. These results suggest that SA-triggers renal injury through oxidative stress and ferroptosis, driven by the suppression of the Nr …

The independent contribution of brain, spinal cord and gadolinium MRI in treatment decision in multiple sclerosis: A population-based retrospective study.

BACKGROUND: Spinal cord and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) can provide additional information to brain MRI to det … with disease modifying treatment (DMT) prescription (n = 6,161). DMTs were classified as platform (dimethyl fumarate, glatiramer acetate, interferon-beta, peg-interferon-beta, teriflunomide), or high-efficacy (alemtuzumab, cladribine, fingolimod, natalizumab, ocrelizumab). We evaluated the association between binary MRI variables and switch from platform to high-e …

Electrophiles modulate glutathione reductase activity via alkylation and upregulation of glutathione biosynthesis.

Cells evolved robust homeostatic mechanisms to protect against oxidation or alkylation by electrophilic species. Glutathione (GSH) is the mo … the electrophilic Nrf2 activators bardoxolone-imidazole (CDDO-Im), bardoxolone-methyl (CDDO-Me) and dimethyl fumarate (DMF) also upregulated GSH biosynthesis while promoting GSSG accumulation, but without directly inhibiting GR activity. In vitro assays in which GR was treated with increasing GSH concentrations and GSH depletion experiments in cells revealed that G …

Role of Nrf2 Signaling in the Regulation of Vascular BK Channel β1 Subunit Expression and BK Channel Function in High-Fat Diet-Induced Diabetic Mice.

The large conductance Ca2+-activated K+ (BK) channel β1-subunit (BK-β1) is a key modulator of BK channel electrophysiology and the downregul … K-β1-mediated channel activation was diminished in HFD mice. Importantly, the activation of Nrf2 by dimethyl fumarate significantly reduced the body weight and blood glucose levels of HFD mice, enhanced BK-β1 transcription, and attenuated MuRF1-dependent BK-β1 protein degradation, which in turn restored coronary BK channel function and BK channel-mediated coronary …

Nuclear factor erythroid 2-related factor 2 is a critical target for the treatment of glucocorticoid-resistant lupus nephritis.

BACKGROUND: Dimethyl fumarate (DMF), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, has been proven effective for the systemic treatment of multiple sclerosis. The aim of this study is to evaluate the anti-inflammatory effects of Nrf2 activators on human renal mesangial cells (HRMCs) and the development of lupus nephritis (LN) in mice. METHODS: To assess Nrf2 activation in vitro, HRMCs were treated with safe doses of Nrf2 activators and prednisolone. The expression levels of Nrf2 and its target genes were measured using quantitative reverse transcription PCR and enzyme-linked…

Sulforaphane-Mediated Multitarget Therapeutic Effects in Methylmercury-Induced ALS-Like Pathology: Comparative Analysis and Multifaceted Approach to Neuroprotection and Systemic Recovery.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by motor neuron loss driven by oxidative stress, neuroinflammation, and dysregulated survival signaling. The objective of this study was to evaluate the neuroprotective efficacy and safety of sulforaphane (SUFP) in a methylmercury (MMHg⁺)-induced preclinical rat model of ALS, with comparison to omaveloxolone (OVX) and dimethyl fumarate (DIMT). SUFP treatment, particularly at 4 mg/kg, significantly restored antioxidant defense mechanisms through upregulation of Nrf2, HO-1, and SIRT1 while suppressing pro-infl…