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Potential Benefits of Nrf2/Keap1 Targeting in Pancreatic Islet Cell Transplantation.

Permanent pancreatic islet cell destruction occurs in type 1 diabetes mellitus (T1DM) through the infiltration of inflammatory cells and cyt … present the most recently studied Nrf2/Keap1 activators in pancreas for application in ICT: Dh404, dimethyl fumarate (DMF), and epigallocatechin gallate (EGCG). Furthermore, we discuss that Nrf2/Keap1 is a potential target to ameliorate oxidative stress at every step of the Edmonton Protocol.

Lipopolysaccharide Binding Protein and Oxidative Stress in a Multiple Sclerosis Model.

Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that altering certain bacterial populations present in the gut ma … ) MS patients were used. In addition, EAE rats were treated with Natalizumab, N-acetyl-cysteine and dimethyl fumarate. Natalizumab was also employed in RRMS. The results of this study revealed an improvement in the clinical symptoms of the EAE and MS with the treatments, as well as a reduction in the oxidative stress parameters and in LBP. Correlations between the …

Effect of teriflunomide on QuantiFERON-TB Gold results.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by damage to myelin and axons, over time leading to progressive neuronal degeneration and microglial activation. There is still no curative treatment, but during the last 20 years eight different therapies have become available including interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab, fingolimod, alemtuzumab, mitoxantrone and teriflunomide. Teriflunomide is an immunomodulatory drug that exerts an inhibitory effect on T cell activation in central nervous system of…

Matrine induces cardiotoxicity by promoting ferroptosis through the Nrf2 antioxidant system in H9c2 cells.

Matrine (MT) has shown promising efficacy in various cancers and chronic hepatitis; however, its clinical application is limited because of … riptional activity of Nrf2 while increasing TFR1 protein levels. Supplementation with Nrf2 agonist (Dimethyl fumarate, DMF) or selenium (Sodium selenite, SS) and CoQ10 alleviated MT-induced cytotoxic effects in H9c2 cells. These results suggest that ferroptosis, which is mediated by an imbalance in the Nrf2 antioxidant system, is involved in MT-induced cardiac toxi …

Cluster Headache as the Index Event in MS: A Case Report.

We report a 42-year-old woman who presented with cluster headache (CH) in association with other neurological symptoms as the index event of new onset multiple sclerosis (MS). Her initial symptoms were left-sided headache with ipsilateral lacrimation and nasal congestion associated with ipsilateral facial numbness. A subsequent similar headache attack was also associated with ipsilateral arm ataxia and gait ataxia. She had many additional short headache attacks without focal neurological symptoms. Her cluster-like headache attacks have not recurred since intiation of dimethyl fumarate. Our pat…

Терапевтические достижения в педиатрии с множественным склерозом.

Педиатрический множественный склероз (POMS) является хроническим и иммунным расстройством, которое влияет на центральную нервную систему детей и подростков. Примерно 3-10% пациентов, страдающих синдромом MS, имеют место до достижения 18-летнего возраста. Подавляющее большинство случаев заболевания педиатрическим синдромом MS характеризуется повторной эрозией с высоким уровнем заболеваемости. Пациенты педиатрии, страдающие синдромом MS, традиционно проходили лечение без маркировки с различной степенью успеха. С одобрением многих новых методов лечения для взрослых МР быстро начали появляться аль

Совпадение в аннотации оригинала
Pediatric-onset multiple sclerosis (POMS) is a chronic, immune-mediated disorder that affects the central nervous system in children and ado … the seminal trials of PARADIGMS, which evaluated fingolimod use in pediatric MS patients, CONNECT (dimethyl fumarate), TERIKIDS (teriflunomide), OPERETTA I (ocrelizumab), and LEMKIDS (alemtuzumab). We will also review the safety and efficacy of different monoclonal antibodies that are commonly prescribed for multiple sclerosis. We will then examine induction versu …

Natalizumab-PML survivors with subsequent MS treatment: Clinico-radiologic outcome.

OBJECTIVE: To describe the clinico-radiologic outcome of MS patients with natalizumab-related progressive multifocal leukoencephalopathy (Nz … Expanded Disability Status Scale at the last follow-up. No relapse was reported with fingolimod and dimethyl fumarate. No radiologic worsening of Nz-PML lesion was observed at the end of the follow-up. CONCLUSION: In this large cohort of patients with Nz-PML, MS therapies given after Nz discontinuation were not associated with PML worsening. A larger cohort with l …

Treatment-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: A Comprehensive Review of Current Evidence and Future Needs.

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system caused by the John Cunningham virus (JCV) that has been associated with therapeutic immunosuppression in patients with multiple sclerosis (MS). So far, more than 600 cases of PML have been reported in association with natalizumab administration. There have also been confirmed cases of PML in individuals who received fingolimod and dimethyl fumarate without previous natalizumab treatment. The new licensed disease-modifying therapies for MS carry the risk of immunosuppressant and so o…

Pyroptosis Drives the Impairment of Colonic Barrier Integrity During Toxoplasma Gondii Chronic Infection.

Toxoplasma gondii (T. gondii) impairs gut barrier integrity in hosts, which helps the establishment of long-term infection and is closely as … iated protein 3), Caspase-1, gasdermin D (GSDMD), GSDMD-N, as well as IL-1β and IL-18. In addition, dimethyl fumarate, an anti-pyroptogenic drug, significantly attenuated the infection-induced pyroptosis and colonic pathology. Notably, macrophages exhibited pyroptosis post T. gondii infection, which was attenuated by DMF treatment. Overall, our results uncover that …

Concurrent targeting of glycolysis in bacteria and host cell inflammation in septic arthritis.

Intracellular infiltration of bacteria into host cells complicates medical and surgical treatment of bacterial joint infections. Unlike soft … matory cascades that persist after conventional antibiotic treatment. The glycolysis-targeting drug dimethyl fumarate (DMF) showed both bacteriostatic and anti-inflammatory effects by hindering the proliferation of intracellular MRSA and dampening excessive intraarticular inflammation. Combinatorial treatment with DMF and vancomycin further reduced the proliferatio …

Multiple sclerosis in a young woman with sickle cell disease.

BACKGROUND: Comorbidities can impose diagnostic and treatment challenges in patients with multiple sclerosis (MS). Sickle cell disease (SCD) … considered. Finally, we discuss innovative pre-clinical research that suggests that natalizumab or dimethyl fumarate may ameliorate SCD symptoms while preventing MS relapses; human trials, however, are needed. CONCLUSION: The co-occurrence of inflammatory disorders, in this case MS and SCD, requires providers to appropriately manage each condition with considerat …

Amelioration of inflammation through reduction of oxidative stress in rheumatoid arthritis by treating fibroblast-like synoviocytes (FLS) with DMF-loaded PLGA nanoparticles.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory condition, and Dimethyl fumarate (DMF) is known for inducing antioxidant enzymes and reducing reactive oxygen species (ROS). Fibroblast-like synoviocytes (FLS) contribute to joint damage by releasing interleukins (IL-1β, IL-6, and IL-8) in response to ROS. Given ROS's impact on FLS acquiring an invasive phenotype, our study explored the effects of poly lactic-co-glycolic acid (PLGA) nanoparticles containing DMF on the expression of the HO-1 enzyme and the inflammatory cytokines IL-1β, IL-6, and IL-8 in FLS cells. METHO…

Post marketing new adverse effects of oral therapies in multiple sclerosis: A systematic review.

BACKGROUND: There is a lack of safety information about the post-marketing adverse effects of several disease-modifying drugs (DMDs) used to … review. The most side effects were observed with fingolimod and teriflunomide, respectively, while dimethyl fumarate had minor side effects. CONCLUSION: The oral therapies have some significant post-marketing adverse effects that have been diagnosed in numerous case reports. Some of them are serious and must be noticed by neurologists. Accordingly, in this review …

Serum Levels of CXCL13 Are Associated With Teriflunomide Response in Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: To identify biomarkers associated with treatment response in patients with multiple sclerosis (MS) treated with the oral therapies teriflunomide, dimethyl fumarate (DMF), and fingolimod. METHODS: Serum levels of IL-6, IL-17, TNF-α, granulocyte-macrophage colony-stimulating factor, IL-10, interferon-gamma (IFN-γ) IL-1β, and chemokine ligand 13 (CXCL13) were measured at baseline and 12 months with single molecule array (Simoa) assays in a cohort of patients with MS treated with teriflunomide (N = 19), DMF (N = 22), and fingolimod (N = 25) and classified into "no evide…

Dimethyl itaconate attenuates IL-1-induced IVIG-resistant inflammation in a coronary artery cell model of Kawasaki disease.

Kawasaki disease (KD) is the most common childhood vasculitis. Approximately 25% of KD patients are refractory to standard intravenous immun … f itaconate, can significantly suppress IL-1β-induced IκBζ expression in HCAECs. DI is an analog of dimethyl fumarate (DMF), which is already in clinical use for some diseases. Like DI, DMF suppressed IL-1β-induced IκBζ expression and subsequent production of inflammatory cytokines, including IL-6 and G-CSF. This study identified IκBζ as an essential inflammatory f …

[Efficacy and safety profile of fumaric acid esters in oral long-term therapy with severe treatment refractory psoriasis vulgaris. A study of 83 patients].

The therapeutic effect and the side of effects fumaric acid derivatives used in treatment of psoriasis vulgaris have been subjects of controversy for more than 30 years. A total of 83 patients with severe psoriasis vulgaris were investigated in a single-centre, long-term open (12 months) clinical trial to evaluate the efficacy and safety profile of the fumaric acid ester preparations Fumaderm initial and Fumaderm. The antipsoriatic effect of the fumaric acid derivatives was clear, with a mean reduction of 76% in PASI. Adverse events in were noted in 62% of the patients (mainly flushing and gas

Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis.

BACKGROUND: BG-12 (dimethyl fumarate) is in development as an oral treatment for relapsing-remitting multiple sclerosis, which is commonly treated with parenteral agents (interferon or glatiramer acetate). METHODS: In this phase 3, randomized study, we investigated the efficacy and safety of oral BG-12, at a dose of 240 mg two or three times daily, as compared with placebo in patients with relapsing-remitting multiple sclerosis. An active agent, glatiramer acetate, was also included as a reference comparator. The primary end point was the annualized relapse rate over a period of 2 years. The …

DMF-Activated Nrf2 Ameliorates Palmitic Acid Toxicity While Potentiates Ferroptosis Mediated Cell Death: Protective Role of the NO-Donor S-Nitroso-N-Acetylcysteine.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease that can develop into an aggressive form called nonalco … μM erastin or 5 μM RSL3 for ferroptosis. In SFA-lipotoxicity, pretreatment with the Nrf2 activator dimethyl fumarate (DMF) managed to ameliorate the cells and the oxidative stress level while aggravating ferroptosis due to emptying the thiol pool. On the other hand, the nitric oxide (NO)-donor, S-nitroso-N-acetylcysteine (NAC-SNO) proved to be effective in the pre …

Activation of Nrf2 by sulfuretin stimulates chondrocyte differentiation and increases bone lengths in zebrafish.

Elongation of most bones occur at the growth plate through endochondral ossification in postnatal mammals. The maturation of chondrocyte is … induced the expression of chondrocyte markers. Consistently, a clinically available Nrf2 activator, dimethyl fumarate (DMF), induced the expression of hypertrophic chondrocyte markers and increased the body length of zebrafish. Importantly, we found that chondrocyte gene expression in cell culture and skeletal growth in zebrafish stimulated by sulfuretin were signi …

[Therapeutic Strategies and Disease-Modifying Therapies for Multiple Sclerosis].

Multiple sclerosis is an inflammatory demyelinating disease of unknown cause that affects the central nervous system. Although it was once d … h- (fingolimod, ofatumumab, natalizumab) or moderate-efficacy (interferon beta, glatiramer acetate, dimethyl fumarate), and there are also disease-modifying therapies for secondary progressive multiple sclerosis (siponimod and ofatumumab). Approximately 20,000 Japanese patients have multiple sclerosis, and this number continues to increase. Many neurologists are ex …