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Identification of anti-inflammatory drugs according to their capacity to suppress type-1 and type-2 T cell profiles.

BACKGROUND: Down-regulation or modulation of T cell activity by immunosuppressive drugs is an effective treatment in diseases where exaggerated T cell responses play a role. A primary effect of the anti-inflammatory drugs (AIDs) is inhibition of the synthesis of growth factors, such as IL-2, thereby down-regulating T cell proliferation. However, it is still largely unknown to what extent these AIDs are able to down-regulate specifically type-1 or type-2 T cell cytokine production, and whether they can down-modulate chemokine receptor expression, thereby preventing migration of T cells to the s

Plasma микроRNA Подпись как предсказательный знак клинической реакции на терапию во время множественного склероза.

ЦЕЛЬ: Несмотря на наличие эффективных методов лечения множественного склероза (MS), непредсказуемый характер развития заболеваний и изменчивость результатов индивидуального лечения требуют надежных биомаркеров. Цель этого экспериментального исследования заключается в изучении потенциала плазмы, циркулирующей микроРНК (миРНК), в качестве биомаркеров-метилфумаратов для клинической реакции на диметил-фумарат (ДМП), широко применяемой пероральной обработки НР. МЕТОДЫ: Образцы периферальной крови были взяты из nineteen лиц с повторными выбросами MS (PwRRMS) до и после 3, 6, 12, и 24 месяцев управле

Совпадение в аннотации оригинала
OBJECTIVE: Despite the availability of effective therapies for Multiple Sclerosis (MS), the unpredictable nature of disease progression and … tential of plasma circulating microRNAs (miRNAs) as predictive biomarkers for clinical responses to dimethyl fumarate (DMF), a widely used oral treatment for MS. METHODS: Peripheral blood samples were collected from nineteen treatment-naïve people with relapsing-remitting MS (pwRRMS) before and after 3, 6, 12, and 24 months of DMF administration, as well as from n …

GSDMD-mediated pyroptosis in the dorsal hippocampus is implicated in morphine-induced reward memory in mice.

Opioid addiction involves maladaptive neuroplasticity within hippocampal circuits, yet the underlying molecular mechanisms remain incomplete … intensity within CA3 neuronal populations. Pharmacological inhibition of GSDMD pore formation with dimethyl fumarate (DMF) not only attenuated morphine-induced CPP but also reversed the upregulation of pyroptotic markers in dHip neurons. Complementary in vitro experiments in HT-22 hippocampal neuronal cells confirmed that morphine directly induces dose-dependent u …

T-2 Toxin Neurotoxicity: Molecular Mechanisms and Emerging Chemoprotective Strategies.

Mycotoxins can contaminate food and raw food materials and are a threat to animal and human health. T-2 toxin is the most toxic secondary me … small inhibitors and nature products, such as daucosterol, betulinic acid, AHN 1-055 hydrochloride, dimethyl fumarate and minocycline supplementations, can partly ameliorate these harmful effects. This review provides valuable insights into the underlying mechanisms of T-2 toxin-induced neurotoxicity and novel effective detoxification strategies.

Emodin, a Potent Anthraquinone Mitigates MPTP-Induced Parkinsons' Disease Pathology by Regulating Nrf2 and Its Downstream Targets: In Silico and In Vivo Approach.

Parkinson's disease (PD) is marked by neurodegeneration that follows the destruction of dopaminergic neurons, mainly localized to the substa … here MPTP-induced PD mice were treated with emodin, and additional groups received Nrf2 modulators: dimethyl fumarate (DMF) as an agonist and all-trans retinoic acid (ATRA) as an antagonist. Emodin treatment led to a significant upregulation of Nrf2 expression, a reduction in oxidative stress markers such as malondialdehyde, and notable improvements in motor and co …

Reprogramming Macrophage Phenotype Using a Reactive Oxygen Species-Responsive Liposome Delivery System for Inflammation Microenvironment Remodeling and Osteoarthritis Treatment.

The progression of osteoarthritis (OA) is closely linked to synovial inflammation caused by an imbalance between M1 and M2 macrophages. To tackle this problem, we developed a liposome responsive to reactive oxygen species (ROS), modified with folic acid ligands to target M1-polarized macrophages, and loaded with the anti-inflammatory agent dimethyl fumarate (DMF). This liposome-based drug delivery system was designed to reprogram macrophage phenotype to remodel the inflammatory microenvironment in the joint cavity and alleviate OA degeneration. The liposome we prepared had a suitable size and …

Воздействие усталости на качество жизни взрослых с множественным склерозом.

ВВЕДЕНИЕ: Усталость при множественном склерозе (МС) определяется как отсутствие физической и/или психической энергии, воспринимаемой человеком, которая препятствует нормальной деятельности. Это самый распространенный симптом в MS, присутствующий до 90% людей с MS. Усталость наряду с инвалидностью, депрессией, когнитивным расстройством и корректирующей болезнь терапией влияет на качество жизни (QoL). МЕТОД: Мы разработали перспективное обследование пациентов с MS и DMT умеренной эффективности для оценки связи между усталостью и эпидемиологическими, клиническими и фармакологическими аспектами, в

Совпадение в аннотации оригинала
INTRODUCTION: Fatigue in multiple sclerosis (MS) is defined as the lack of physical and/or mental energy perceived by the individual that in … years. The DMT were: 27.4% interferon-β, 15.38% glatiramer acetate, 9.89% teriflunomide, and 47.25% dimethyl fumarate. The median of the EDSS was 1.5 points. 40.9% have presented fatigue, 36.3% cognitive deterioration and 30.7% of the patients depression. CONCLUSIONS: Patients with fatigue are older, more disabled, have a higher prevalence of depression and worse …

Значительная отмена множественных склерозов в модели мыши EAE с использованием PC-210 Aminothiol.

Множественный склероз (MS) — сложное заболевание, характеризующееся хронической нейроинфламмацией и реактивной токсичностью кислорода (ROS) в центральной нервной системе (CNS). Основываясь на этом механизме ROS, мы проверили, сможет ли PC-210-а новый аминотиол ROS-поглотить симптомы MS в мышах с экспериментальным аутоиммунным энцефаломиелитом (EAE) MS. Наши цели заключались в том, чтобы оценить роль РСО в РС и потенциальные выгоды от РЦ-210 для управления НР. Мыши с EAE получили различные дозы PrC-210 по профилактическим и терапевтическим протоколам. Динамика заболевания измерялась с помощью к

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a complex disease marked by chronic neuroinflammation and reactive oxygen species (ROS) toxicity in the central n … afety was assessed by comparing the gastrointestinal and hematological toxicity between PrC-210 and dimethyl fumarate (DMF, Tecfidera's active agent). PrC-210 reduced MS severity by up to 62% in paralysis scores versus those in the controls (p = 0.0001), whether used preventively or at the onset of paralysis. The group with the greatest decrease also showed the bes …

Безопасность и эффективность opicinumab у участников с повторным множественным склерозом (AFFINITY Part 1: случайный, контролируемый, этап 2.

Опицинумаб, человек-моноклональная антитела против ЛИНПО-1, гипотетизируется в целях поощрения ремиэлизации путем усиления дифференциации клеток потомков олигодендроцитов. ЦЕЛЬ: Цель исследования заключается в изучении эффективности и безопасности opicinumab в качестве дополнительного средства лечения против воспаления заболеваний (ДМТ) у участников с повторным множественным склерозом (RMS). МЕТОДЫ: Участники РМС в возрасте 18-58 лет с продолжительностью болезни до 20 лет были случайными: 1:1 для получения внутривенных вливания плацебо или opicinumab каждые 4 недели в течение 72 недель. Первос

Совпадение в аннотации оригинала
BACKGROUND: Opicinumab, a human monoclonal antibody against LINGO-1, is hypothesized to promote remyelination by enhancing the differentiati … 0 years with Expanded Disability Status Scale ⩾ 3.0, with disease duration ⩾ 6 years, and receiving dimethyl fumarate as the background DMT. 85% participants in placebo group and 86% in opicinumab group had adverse events. CONCLUSION: Although the AFFINITY study did not show significant difference in mean ODRS between opicinumab and placebo groups, data from AFFIN …

Fingolimod и риск заболевания раком кожи у лиц с множественным склерозом: протокол когортного исследования на основе популяции.

ВВЕДЕНИЕ: Для изучения последствий рака кожи у лиц с множественным склерозом (MS), обработанных финголимодом, необходимы долгосрочные исследования по вопросам безопасности населения с применением передовых методов установления причинно-следственных связей, в том числе с активным компаратором с дизайном новых пользователей. Цель этого исследования состоит в том, чтобы охарактеризовать протокол изучения взаимосвязи между использованием финголимодов и заболеваемостью раком кожи у лиц с НР. МЕТОДЫ И АНАЛИЗ: Мы будем использовать данные об административном здоровье населения из двух канадских прови

Совпадение в аннотации оригинала
INTRODUCTION: Long-term population-based safety studies, applying advanced causal inference techniques, including an active comparator with … validated algorithm. Incident users of fingolimod and active comparators (natalizumab, alemtuzumab, dimethyl fumarate, teriflunomide) will then be identified. The outcome of interest will be skin cancer (melanoma and non-melanoma skin cancers). Survival analysis will be used to estimate HRs and corresponding 95% CIs, adjusted for potential confounders. ETHICS AND …

Оптимизация лечения педиатрического множественного склероза.

ВВЕДЕНИЕ: Педиатрический множественный склероз (POMS) отличается от взрослых MS в своих клинических характеристиках и курсах по болезням. В ПОМС наблюдается повышенная подстрекательская активность с более высокими показателями рецидивов и травмирования, наряду с менее ранними физическими недостатками, но более выраженными когнитивными нарушениями и ухудшением роста мозга. ОБЛАСТЬ ПРИМЕНЕНИЯ: В настоящем обзоре рассматривается стратегия обработки в рамках ПОМС на основе данных о безопасности и эффективности наблюдений и выборочных контролируемых испытаний. Эта статья основана на результатах пои

Совпадение в аннотации оригинала
INTRODUCTION: Pediatric-onset multiple sclerosis (POMS) differs from adult MS in its clinical characteristics and disease course. POMS exhib … ty of life.Low/moderate-efficacy therapies, such as interferons, glatiramer acetate, teriflunomide, dimethyl fumarate should be reserved for patients with mild disease. While long-term safety data, personalized prognostic markers and de-escalation strategies are still needed, high-efficacy therapies provide a promising standard of care, especially given enhanced ne …

RANK/RANKL axis promotes migration, invasion, and metastasis of osteosarcoma via activating NF-κB pathway.

Osteosarcoma (OS) is one of the most prevalent primary bone tumors with a high degree of metastasis and poor prognosis. Epithelial-to-mesenc … uces EMT by activating the nuclear factor-kappa B (NF-κB) pathway. Furthermore, the NF-κB inhibitor dimethyl fumarate (DMF) suppressed migration, invasion, and EMT in OS cells. Our results suggest that the RANK/RANKL axis may serve as a potential tumor marker and promising therapeutic target for OS metastasis. Furthermore, DMF may have clinical applications in the …

Use of multiple sclerosis disease-modifying therapies during pregnancy in France: Nationwide study between 2010 and 2021.

BACKGROUND: Multiple sclerosis (MS) frequently affects women of childbearing age and pregnant women. OBJECTIVE: To assess the use of MS dis … 010-2012 to 2413 in 2019-2021 (+124%), especially those exposed to glatiramer acetate, natalizumab, dimethyl fumarate, and anti-CD20. Among pregnancies of women on DMT 6 months before pregnancy, 78.0% underwent DMT discontinuation and 7.6% switched DMT, generally before (33.0% and 77.0%, respectively) or during the first trimester of pregnancy (58.3% and 17.8%, res …

Gain-of-function variants in GSDME cause pyroptosis and apoptosis associated with post-lingual hearing loss.

Gasdermin E (GSDME), a member of the gasdermin protein family, is associated with post-lingual hearing loss. All GSDME pathogenic mutations … positive feedback on the cleavage of GSDME. Furthermore, we found that treatment with disulfiram or dimethyl fumarate might inhibit pyroptosis and apoptosis by inhibiting the release of GSDME-N from GSDME mutants. In conclusion, this study elucidated the molecular mechanism associated with hearing loss caused by GSDME gene mutations, offering novel insights for pot …

Overview of emerging therapies for demyelinating diseases.

This paper provides an overview of autoimmune disorders of the central nervous system, specifically those caused by demyelination. We explor … ute disseminated encephalomyelitis. Beyond these emerging systemic therapies, we also introduce the dimethyl fumarate/silk fibroin nerve conduit and its potential role in the treatment of peripheral nerve injuries. Despite these aforementioned scientific advancements, this paper maintains the need for ongoing research to deepen our understanding of demyelinating di …

Финголимод-ассоциированная центральная серьёзная ретинопатия, представляющая восемь лет после лечения: доклад по делу.

Fingolimod — это эффективный вариант лечения при управлении множественным склерозом, в то время как его применение связано с изменяющимися окулярными негативными последствиями. Здесь мы представляем пример развития центральной серозной ретинопатии (КСО) в долгосрочной перспективе после начала лечения фенолимодом. 53-летняя женщина с повторно излучающимся множественным склерозом с метеморфопсией в левом глазу. Медицинская история показала, что пациент восемь лет лечился фенолимодом. Офтальмологический анализ показал, что сетчатки указывают на изменения в КСО. Учитывая необходимость продолжения

Совпадение в аннотации оригинала
Fingolimod is an efficacious treatment option in the management of multiple sclerosis, while variable ocular adverse effects have been assoc … nted with recurrence of fluid in the subRPE level. Thereafter, fingolimod treatment was switched to dimethyl fumarate. The patient's condition remained clinically stable without recurrence of fluid during a three-month follow-up period. Our case provides insight into the fingolimod associated retinal findings manifesting as CSR changes, indicating that ocular compl …

Caffeic acid, but not ferulic acid, inhibits macrophage pyroptosis by directly blocking gasdermin D activation.

Regulated pyroptosis is critical for pathogen elimination by inducing infected cell rupture and pro-inflammatory cytokines secretion, while … ls of interleukin-1β and tumor necrosis factor-α as the known pyroptosis inhibitors, disulfiram and dimethyl fumarate. Collectively, these findings suggest that CA inhibits pyroptosis by targeting GSDMD and is a potential candidate for curbing the pyroptosis-associated disease.

Monosodium Urate Crystal-Induced Pyroptotic Cell Death in Neutrophil and Macrophage Facilitates the Pathological Progress of Gout.

Monosodium urate (MSU) crystal deposition in joints can lead to the infiltration of neutrophils and macrophages, and their activation plays … 1β). Based on these mechanistic understandings, it is shown that N-GSDMD oligomerization inhibitor, dimethyl fumarate (DMF), inhibits MSU crystal-induced pyroptosis in BMNs and J774A.1 cells, and it further alleviates the acute inflammatory response in MSU crystals-induced gout mice model. This study elucidates that MSU crystal-induced pyroptosis in neutrophil and …

Simultaneous intervention against oxidative stress and inflammation by targeting Nrf2/ARE and NLRP3 inflammasome pathway mitigates thioacetamide-induced liver fibrosis in rat.

Liver fibrosis is a typical pathological state/stage involved in most chronic liver diseases and its persistence results in cirrhosis. Inflammasomes are cytoplasmic sensors that induce inflammation in response to stress. Glibenclamide (GLB) is an USFDA-approved drug for type 2 diabetes and is reported to possess anti-inflammatory activity by inhibiting inflammatory cytokines. Dimethyl fumarate (DMF) is an USFDA-approved drug for multiple sclerosis and has been reported to activate the Nrf2/ARE pathway to maintain the cellular antioxidant balance. A total of 36 rats were randomized into six gro…

Anti-IL23for nail psoriasis in real life: Results of efficacy and safety during a 52-week period.

Nail psoriasis (NP) is often considered disfiguring for patients with a relevant impact on quality of life (QoL). It is also difficult to treat for dermatologists who are often frustrated by the scarcity of effective therapeutic alternatives in this particular location. Topical therapies are often used as the first-line treatment for mild NP, but efficacy is the modest. Conventional disease-modifying antirheumatic drugs (cDMARDs) (e.g., cyclosporine, methotrexate, acitretin, and dimethyl fumarate) are generally avoided in NP without general cutaneous involvement. Biologics represent, to date, …