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Risks vs benefits of glatiramer acetate: a changing perspective as new therapies emerge for multiple sclerosis.

An understanding of the risks, benefits, and relative value of glatiramer acetate (GA) in multiple sclerosis (MS) has been evolving based on … emerging therapies (cladribine, alemtuzumab, rituximab, fingolimod, laquinimod, teriflunomide, and dimethyl fumarate) based on phase II/III trials, as well as their use for indications other than MS, will be presented. This review provides available data on GA, natalizumab, and the emerging agents to support new developments in our understanding of GA and how its …

Oxidative Stress and NRF2-Mediated Redox Regulation in Incomplete Systemic Lupus Erythematosus and Systemic Lupus Erythematosus.

Oxidative stress plays an important role in systemic lupus erythematosus (SLE). To elucidate whether it is already present in early phases, … hermore, PBMCs and HaCaT keratinocytes were treated with the NRF2 activators sulforaphane (SFN) and dimethyl fumarate (DMF) in vitro to assess expression of antioxidant genes. Finally, NRF2 and Heme oxygenase-1 (HMOX1) proteins in non-sun-exposed skin sections were assessed. Thiols were significantly lower in qSLE patients compared to HCs. In whole blood, Kelch-lik …

Vitamin D Promotes Neuronal Survival via Nrf2 Upregulation in D-Galactose-Induced Mice: An In-Vivo and In-Silico Study.

Gradual loss of the homeostatic balance owing to deregulation of endogenous antioxidant defense pathways, such as nuclear factor erythroid 2 … athione peroxidase (GPx), and upregulating Nrf2 and HO-1 expression comparable to positive control, dimethyl fumarate (DMF). Co-administration of all-trans retinoic acid (ATRA), an antagonist for Nrf2, abrogated these protective effects, confirming the pathway specificity. Molecular docking studies have shown a strong binding affinity of Vitamin D to the regulatory …

Differential safety profiles of disease-modifying therapies in MS: Age- and sex-based analysis from a real-world cohort.

BACKGROUND/OBJECTIVES: Age and sex may modulate adverse events (AE) under disease-modifying therapies (DMTs) in Multiple Sclerosis (MS), yet comparative real-world data across agents remain limited. We assessed age- and sex-specific adverse event (AE) patterns within individual disease-modifying therapy (DMT) cohorts (dimethyl fumarate, fingolimod, natalizumab, and ocrelizumab) in a real-world setting. METHODS: Demographics, EDSS, laboratory parameters (CBC, LFTs, immunoglobulins), infections (PCR/culture), and first-dose ECG/HR were extracted for single-centre retrospective cohort (2010-2021…

Влияние различных методов лечения на толщину спины у пациентов с множественным склерозом: обзор.

Множественный склероз (MS) — аутоиммунное расстройство, воздействующее на центральную нервную систему с различными клиническими проявлениями, такими, как оптический неврит, сенсорные расстройства и синдромы головного мозга. Происхождение заболеваний контролируется с помощью таких методов, как сканирование МРТ, шкала инвалидности и томография оптической согласованности (OCT), которые могут обнаруживать утончённую сетчатку сетчатки, даже при отсутствии оптического невраита. MS прогрессирует в нейродегенерации, особенно транссинптической дегенерации, которая выходит за рамки первоначального места

Совпадение в аннотации оригинала
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disorder affecting the central nervous system, with varying clinical manifestations suc … a relatively modest impact on retinal atrophy. Oral medications like Fingolimod, Teriflunomide, and Dimethyl fumarate also have different impacts on retinal thickness. Fingolimod has been shown to protect against retinal thinning but may lead to macular edema. DMF-treated patients had less ganglion cell-inner plexiform layer thinning than GA-treated patients but mo …

Five-year efficacy outcomes of ocrelizumab in relapsing multiple sclerosis: A propensity-matched comparison of the OPERA studies with other disease-modifying therapies in real-world lines of treatments.

BACKGROUND: Clinical trials comparing the efficacy of ocrelizumab (OCR) with other disease-modifying therapies (DMTs) other than interferon (IFN) β-1a in relapsing multiple sclerosis (RMS) are lacking. OBJECTIVES: To compare the treatment effect of OCR vs six DMTs' (IFN β-1a, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, natalizumab) treatment pathways used in clinical practice by combining clinical trial and real-world data. METHODS: Patient-level data from OPERA trials and open-label extension phase, and from the German NeuroTransData (NTD) MS registry, were used to bui…

Recent advances in noninvasive assessment of liver steatosis.

BACKGROUND: PM2.5 is a well-known harmful air pollutant that can lead to acute exacerbation and aggravation of respiratory diseases. Althoug … and the degradation of Keap1 in PM2.5-exposed BEAS-2B cells. Moreover, we found that quercetin and dimethyl fumarate markedly decreased lipid peroxidation production and ferroptosis by activating the Nrf2-Keap1 pathway in PM2.5-exposed cells. Furthermore, quercetin reduced inflammatory cytokines and TGF-β1 in PM2.5-exposed cells. CONCLUSION: Our data suggested th …

[Translated Article] Disease-modifying treatments for patients with multiple sclerosis in Spain.

UNLABELLED: Multiple sclerosis is a chronic demyelinating disease of the central nervous system and long-term disabling. Different disease-m … ation was the relapsing remitting form (89.3%). The most prescribed disease-modifying treatment was dimethyl fumarate (19.1%), followed by teriflunomide (14.0%). Of the parenteral disease-modifying treatments, the two most prescribed were glatiramer acetate and natalizumab with 11.1% and 10.8%. 24.7% of the patients had 1 comorbidity and 39.8% had at least 2 comorb …

SARS-CoV-2 mRNA vaccinations fail to elicit humoral and cellular immune responses in patients with multiple sclerosis receiving fingolimod.

BACKGROUND: SARS-CoV-2 mRNA vaccination of healthy individuals is highly immunogenic and protective against severe COVID-19. However, there … alysed, 105 received either anti-CD20-based B cell depletion (aCD20-BCD), fingolimod, interferon-β, dimethyl fumarate, glatiramer acetate, teriflunomide or natalizumab, and 21 were untreated MS patients for comparison. RESULTS: In contrast to all other MS patients, and even after booster, most aCD20-BCD- and fingolimod-treated patients showed no to markedly reduce …

Targeting of GSDMD sensitizes HCC to anti-PD-1 by activating cGAS pathway and downregulating PD-L1 expression.

BACKGROUND: Gasdermin D (GSDMD) is well known as a downstream of inflammasomes. However, the roles of GSDMD itself in hepatocellular carcino … s or metastatic HCC. Combination of anti-programmed cell death protein-1 (PD-1) and GSDMD inhibitor dimethyl fumarate (DMF) was used to test for improved therapeutic efficacy. RNA sequencing was used to explore the mechanisms how GSDMD promoted HCC progression. RESULTS: The expression of GSDMD and GSDMD-N was upregulated in HCC tissues or metastatic HCC tissues an …

Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating central nervous system disease that typically strikes young adults, especial … trials, interferon-beta, glatiramer acetate, mitoxantrone, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, BG-12, alemtuzumab, rituximab, ocrelizumab, daclizumab, neutralizing antibodies, progressive multifocal leukoencephalopathy.

Inhibitory effect of orally administered donepezil hydrochloride (E2020), a novel treatment for Alzheimer's disease, on cholinesterase activity in rats.

Donepezil hydrochloride ((+/-)-2-[(1-benzylpiperidin-4-yl)methyl]-5, 6-dimethoxy-indan-1-one monohydrochloride: E2020: donepezil) is a potent and selective acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease. The present experiments were designed to compare the inhibitory effects of orally administered donepezil and other cholinesterase inhibitors, tacrine (9-amino-1,2, 3,4-tetrahydroacridine hydrochloride), (S)-N-ethyl-3-[(1-dimethyl-amino)ethyl]-N-methyl-phenylcarbamate hydrogentartrate (ENA-713, rivastigmine) and 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4, 5-t

Microglial Nrf2 Activation Orchestrates Ferroptosis Inhibition and α-Synuclein Clearance in Parkinson's Disease.

Parkinson's disease (PD) is pathologically characterized by the abnormal aggregation of α-synuclein and the progressive loss of dopaminergic … elerated α-synuclein aggregation. Conversely, Nrf2 overexpression or pharmacological activation via dimethyl fumarate (DMF) profoundly suppressed α-synuclein pathology and mitigated ferroptosis-associated signatures. In vivo, microglial activation in the substantia nigra of PD mice was accompanied by marked Nrf2 downregulation. Strikingly, microglia-specific Nrf2 o …

Clinical, demographic, and pharmacological predictors of medication adherence to disease-modifying therapies in multiple sclerosis: a multidimensional analysis of merged survey and claims data.

Sustained adherence to disease-modifying therapies (DMTs) is essential for achieving therapeutic benefit in multiple sclerosis (MS). Despite … owed the lowest adherence and teriflunomide, sphingosine-1-phosphate (S1P) receptor modulators, and dimethyl fumarate the highest (all p < 0.001 vs. glatiramer acetate). Demographic, including socioeconomic, and clinical characteristics, comprising age, sex, income, education, employment, MS subtype, disease duration, and disease activity, showed no measurable asso …

Target trial emulation to replicate randomised clinical trials using registry data in multiple sclerosis.

UNLABELLED: BackgroundTarget trial emulation (TTE) offers a formal framework for causal inference using observational data, but its validity … ASSESS (fingolimod vs glatiramer acetate), BEYOND (interferon beta vs glatiramer acetate), CONFIRM (dimethyl fumarate (DMF) vs glatiramer acetate), OPERA (ocrelizumab vs interferon beta), REGARD (interferon beta vs glatiramer acetate), RIFUND-MS (rituximab vs DMF), TENERE (teriflunomide vs interferon beta) and TRANSFORMS (fingolimod vs interferon beta). Treatment e …

HY-021068 improves neuronal ferroptosis by activating Nrf2 signaling in APP/PS1 Mice and Aβ1-42-induced HT22 cells.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with an unclear pathogenesis and no effective treatment methods. HY-021 … the Nrf2 inhibitor ML385 markedly diminished the protective effects of HY, while the Nrf2 activator dimethyl fumarate (DMF) resulted in a significant enhancement of HY's therapeutic effects in Aβ1-42-induced HT22 cells. Molecular docking and cellular thermal shift assay showed that HY had an interaction with Nrf2. These results suggested that HY could ameliorate AD …

Structure-based molecular hybridization design and synthesis of Keap1-Nrf2 inhibitors for anti-inflammatory treatment.

The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway stands as a pivotal mec … gy to design a series of novel naphthalene sulfonamides by combining NXPZ-2 with the Nrf2 activator dimethyl fumarate (DMF) or its analogues. Among these new derivatives, compound 1c, specifically (Z)-4-((4-(N-(2-amino-2-oxoethyl)-N-(4-((N-(2-amino-2-oxoethyl)-4-methoxyphenyl)sulfonamide)naphthalen-1-yl) sulfamoyl)phenyl)amino)-4-oxobut-2-enoic acid, exhibited the …

Cardiovascular safety of systemic psoriasis treatments: A prospective cohort study in the BIOBADADERM registry.

BACKGROUND: Psoriasis is a chronic inflammatory disease with multiple comorbidities, including an increased risk of major adverse cardiovasc … nti-TNF, IL-12/23, IL-17 and IL-23 inhibitors), conventional systemic therapies (MTX, cyclosporine, dimethyl fumarate and acitretin) and apremilast (APR). The IR for each group was compared to those observed in patients treated with MTX using Poisson regression models adjusted for potential confounders, with 95% confidence intervals (95% CI). The primary outcome wa …

Beyond Efficacy: Persistence, NEDA, and Therapeutic Decision-Making in First-Line Multiple Sclerosis Treatment.

INTRODUCTION: Injectable drugs, including interferon-beta and glatiramer acetate (collectively referred to as BRACE), dimethyl fumarate (DMF), and teriflunomide (TER) are commonly used as initial disease-modifying therapies (DMTs) for multiple sclerosis (MS), especially in patients with favorable prognostic profiles. Despite their continued use, real-world comparative data on long-term treatment persistence and comprehensive disease control remain limited. METHODS: This retrospective study analyzed 400 patients initiating BRACE (n = 132), DMF (n = 130), or TER (n = 138) between 2014 and 2024 …

Modulation of Paraoxonase 1 Activity and Asymmetric Dimethylarginine by Immunomodulatory Therapies in Multiple Sclerosis.

Background: Neurodegeneration is present from the earliest stages of multiple sclerosis [MS], and oxidative stress together with mitochondri … ower in MS patients than controls (p < 0.0001) and differed among treatment subgroups (natalizumab, dimethyl fumarate, glatiramer acetate, untreated RRMS). Conclusions: PON1 activity and ADMA levels differ between MS subgroups and under immunomodulatory treatments. Long-term therapy was associated with increased PON1 activity, while highly effective immunomodulator …