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Restoring autophagy-apoptosis balance in diabetic cardiomyopathy via a biomimetic, ROS-responsive nanocarrier associated with Mst1 pathway modulation.

Diabetic cardiomyopathy (DCM) is driven by oxidative stress and an imbalance between autophagy and apoptosis. To improve myocardial delivery of dimethyl fumarate (DMF), a known NRF2-activating redox modulator, and evaluate its association with Mst1 pathway regulation, we developed a cardiac-targeting peptide (APT)-modified biomimetic, reactive oxygen species (ROS)-responsive nanoplatform (NP-APT). NP-APT comprises a ROS-sensitive core and a lipid-cell membrane hybrid coating modified with APT to achieve targeted delivery. The designed nanoplatform demonstrated favorable physicochemical propert…

Caspase-12 exhibits non-redundant functions in response to endoplasmic reticulum stress to promote GSDMD-mediated NETosis, leading to thoracic aortic dissection.

BACKGROUND: Thoracic aortic dissection (TAD) is a highly lethal condition that is characterized by inflammatory cell infiltration. Recent evidence has indicated that Gasdermin D (GSDMD) plays an important role in vascular inflammation and degeneration. However, its effects on neutrophil extracellular trap formation and release (NETosis) during TAD remain unknown. METHODS: A TAD mouse model was generated using four-week-old male neutrophil-specific GSDMD-knockout mice (GSDMDF/F; ElaneCre) and dimethyl fumarate (DMF)-treated C57BL/6J mice by administering β-aminopropionitrile monofumarate (BAPN…

The janus face of astrocytes in multiple sclerosis: Balancing protection and pathology.

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by demyelination and neurodegeneration in the central nervous system … r through neurotrophic factor release (e.g., BDNF, CNTF) and remyelination. Emerging therapies like dimethyl fumarate (DMF) and fingolimod modulate astrocyte reactivity, targeting oxidative stress and sphingosine-1-phosphate receptors to mitigate neuroinflammation. However, challenges persist in translating murine A1/A2 concepts to human MS, as human astrocytes dis …

Analysis of seroconversion following COVID-19 vaccination among multiple sclerosis patients treated with disease-modifying therapies in Poland.

CLINICAL RATIONALE FOR THE STUDY: The rapid spread of SARS-CoV-2 throughout the world has highlighted the importance of vaccinations to cont … ion in PwMS who received immunomodulatory DMTs (interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab) was 91.5%, in PwMS receiving immune reconstruction therapy (alemtuzumab, cladribine) was 92%, and in immunosuppressive DMTs (fingolimod, ocrelizumab), the seroconversion rate was 59%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study s …

Simultaneous Determination of 12 Preservatives in Pastries Using Gas Chromatography-Mass Spectrometry.

(1) Background: Preservatives may pose a potential threat to human health. To ensure food safety, this study has devised a method that concurrently detects a dozen preservatives (acetic acid, propionic acid, dehydroacetic acid, benzoic acid, sorbic acid, dimethyl fumarate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, and isobutyl parahydroxybenzoate) in pastry, utilizing gas chromatography-mass spectrometry. (2) Methods: The pastry samples were acidified with hydrochloric acid, extracted with aceton…

Familial multiple sclerosis in patients with Von Hippel-Lindau disease.

BACKGROUND: Multiple sclerosis (MS) is a progressive autoimmune demyelinating disorder. Recent studies suggest that a combination of genetic … wn to be the primary regulator of Nrf2, the well-established target of the FDA-approved therapeutic dimethyl fumarate. These cases provide support for further studies to determine whether VHLD pathway related genes represent a novel genetic link in multiple sclerosis.

Diagnostic Value of JC Polyomavirus Viruria, Viremia, Serostatus and microRNA Expression in Multiple Sclerosis Patients Undergoing Immunosuppressive Treatment.

Markers of JC polyomavirus (JCPyV) activity can be used to evaluate the risk of progressive multifocal leukoencephalopathy (PML) in treated multiple sclerosis (MS) patients. The presence of JCPyV DNA and microRNA (miR-J1-5p), the anti-JCV index and the sequence of the non-coding control region (NCCR) in urine and plasma were determined in 42 MS subjects before treatment (T0), 6 months (T6) and 12 months (T12) after natalizumab, ocrelizumab, fingolimod or dimethyl-fumarate administration and in 25 healthy controls (HC). The number of MS patients with viruria increased from 43% at T0 to 100% at

LncRNA AFAP1-AS1 mediates therapy-dependent expression of CCL5, CXCL10 and MMP9 in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by inflammation, are … eceiving different treatments (Fingolimod, Interferon beta-1a, Interferon beta-1b, Teriflunomide or Dimethyl fumarate). Our results reported an upstream regulatory effect of AFAP1-AS1 on MMP9, CCL5, and CXCL10 in differently treated patients. By measuring the levels of proteins upon silencing of AFAP1-AS1, it was confirmed that this lncRNA has varying effects on th …

Corynebacterium pseudotuberculosis phospholipase D targets mitochondrial sphingomyelin and induces NLRP3-GSDMD axis-mediated pyroptosis in macrophages to promote infection.

Infection by Corynebacterium pseudotuberculosis (Cp), a facultative intracellular bacterium, causes mainly purulent inflammation and chronic granulomas in animals and humans. Pyroptosis is a proinflammatory form of programmed cell death that is important in response to pathogen infection. The role of pyroptosis in Cp infection and the related mechanisms are still unclear. Here, we reveal that Cp infection induces pyroptosis in macrophages. The inhibition of pyroptosis by disulfiram (DSF) or dimethyl fumarate (DMF) decreases the pathogenicity of Cp in mice and prevents the escape of this pathog…

Стратегии внедрения для повышения фармакологической эффективности модуляторов NRF2: обзор.

Сигнал NRF2/KEAP1 регулирует генное выражение многочисленных цитозащитных и детоксирующих ферментов и поэтому имеет важнейшее значение для поддержания клеточного рентгенокса гомеостаза. Несмотря на растущие знания о том, что NRF2 сигнализирует о сложности, диметилфумарат остается единственной лечебной терапией NRF2-нацеливания в клинической практике, используемой для многократного склероза. Текущие исследования по изучению роли NRF2 в раковых заболеваниях, нейродегенерации, диабете и сердечно - сосудистых заболеваниях, почечных заболеваниях и заболеваниях печени открывают значительные перспект

Совпадение в аннотации оригинала
The NRF2/KEAP1 signaling pathway regulates the gene expression of numerous cytoprotective and detoxifying enzymes and is therefore essential for maintaining cellular redox homeostasis. Despite the increasing knowledge of NRF2 signaling complexity, dimethyl fumarate remains the sole NRF2-targeting therapy in clinical practice, used for multiple sclerosis. Ong…

Обычные, биоаналогичные и последующие небиологические сложные лекарственные средства для многоразового склероза: наглядный обзор нормативных и клинических последствий для европейских нееврологий.

Множественный склероз (МС) создает для пациентов значительное социально-экономическое бремя в связи с его ранним наступлением и прогрессивным характером, однако на системы здравоохранения также влияют высокие издержки, связанные с лечением болезней (ДМТ). Использование непатентованных (для обычных лекарственных средств), биоаналогичных (для биологики) или последующих версий небиологических сложных лекарственных средств (НБЦД) может способствовать снижению стоимости ухода за НР и улучшению доступа пациентов. В настоящем обзоре описываются европейские процессы регулирования этих "копий" DMT и им

Совпадение в аннотации оригинала
BACKGROUND: Multiple sclerosis (MS) places substantial socioeconomic burden on patients due to its early onset and progressive nature, but h … e clinical studies with generic treatments for MS (two with generic fingolimod and one with generic dimethyl fumarate), 11 studies with biosimilars (eight with biosimilar interferon formulations, one with natalizumab and two with rituximab biosimilars) and six studies with follow-on glatiramer acetate. The data showed that the generics, biosimilars and follow-on NB …

Distinct disease-modifying therapies are associated with different blood immune cell profiles in people with relapsing-remitting multiple sclerosis.

Disease modifying therapies (DMTs) used for treating people with relapsing-remitting multiple sclerosis (pwRRMS) target the immune system by … ttern across all therapies in any of the cell populations analysed. PwRRMS treated with fingolimod, dimethyl fumarate (DMF), or alemtuzumab have reduced numbers of CD4+ and CD8+ T cells, as well as Treg subsets, with fingolimod causing the most pronounced decrease in T cell subsets. In contrast, teriflunomide and interferon (IFN) β have minimal impact on T cells, a …

A Case of Erythrodermic Psoriasis Successfully Treated with Risankizumab.

Psoriasis is a chronic inflammatory cutaneous disease, affecting up to 3% of the worldwide population. Several clinical phenotypes can be di … o-severe psoriasis management which relies on the use of conventional systemic drugs (cyclosporine, dimethyl fumarate, methotrexate, retinoids) and biologic agents. However, conventional systemic drugs are often contraindicated for patients' comorbidities, or their use is characterized by reduced efficacy and various adverse events (AEs). The recent development of …

Inflammation and Nitro-oxidative Stress as Drivers of Endocannabinoid System Aberrations in Mood Disorders and Schizophrenia.

The endocannabinoid system (ECS) is composed of the endocannabinoid ligands anandamide (AEA) and 2-arachidonoylgycerol (2-AG), their target … based on these detailed molecular neurobiological mechanisms, it is suggested that cannabidiol and dimethyl fumarate may have therapeutic potential for major depressive disorder, bipolar disorder and schizophrenia.

Long term multiple sclerosis drug delivery using dendritic polyglycerol flower-like microspheres.

The purpose of this study was to produce and characterize the dendritic polyglycerol microspheres (DPGlyM) carrier with potential for use in the treatment of multiple sclerosis (MS). This novel drug delivery system is comprised of DPGlyM as carrier for dimethyl fumarate (DMF) and curcumin (CUR). Molecular docking (MD) was used as in-silico tool to guide the drug entrapment and indicates a spontaneous interactions of DPGlyM with DMF (ΔG° = -11.3 kJ mol-1) and CUR (ΔG° = -23.8 kJ mol-1). The DPGlyM morphology and size distribution were determined using a scanning electron microscopy (SEM). The a…

Oral Disease-Modifying Treatments for Relapsing Multiple Sclerosis: A Likelihood to Achieve No Evidence of Disease Activity or Harm Analysis.

BACKGROUND: The likelihood to help or harm (LHH) is an absolute measure of the benefit versus risk profile of a medication, which can be used to assess the potential for benefit versus harm of different disease-modifying treatments (DMTs) for relapsing multiple sclerosis (R-MS) and facilitate clinical decision-making. OBJECTIVE: The objective of this study was to assess absolute differences in benefit:risk ratios of oral DMTs for R-MS, using LHH analysis with no evidence of disease activity (NEDA) as beneficial outcome. DESIGN/METHODS: The number needed to treat for a paient to achieve NEDA

Comparative Investigation of Cytotoxic Effects of Structurally Diverse Small Molecules and In Silico Analysis of 1-Acetyl-4-(4-Hydroxyphenyl)piperazine.

This study assessed the anticancer activity of boron-containing and structurally diverse small molecules in 4T1 breast cancer and Caco-2 colon adenocarcinoma cells. Initial screening showed that five boronic acids lacked significant cytotoxicity, underscoring the structural specificity required for boron-mediated bioactivity. Similarly, reference compounds, including fumaric acid, caffeic acid, ferulic acid, dimethyl malonate and N-(tert-butoxycarbonyl)-L-alanine, showed no cytotoxic effect under identical conditions. Among the tested agents, 1-acetyl-4-(4-hydroxyphenyl)piperazine (1A4HP) disp

CD20 targeted nanomedicine for GCB-diffuse large B-cell lymphoma through synergistic effects of apoptosis and ferroptosis.

Diffuse large B-cell lymphoma (DLBCL) is one of the most prevalent lymphomas, and can be classified as activated B-cell DLBCL (ABC-DLBCL) or germinal center B-cell DLBCL (GCB-DLBCL) according to molecular subtypes. Studies have shown that drug resistance is an important factor in its therapeutic failure. Tumor-specific drug delivery nanocarriers may be a promising strategy for the treatment of lymphoma. Herein, we developed a nanomedicine (RTX-DOX/DMF-Lip, RDDL) carrying the chemotherapeutic drugs doxorubicin (DOX) and dimethyl fumarate (DMF), and surface-modified with rituximab (RTX), which c…

Preconditioning enhances neurotrophic factor expression in rat bone marrow mesenchymal stem cells for neuroregenerative applications.

Stroke is a leading cause of mortality and disability in adults worldwide. Among the various treatment strategies, cell-based therapies have gained considerable attention due to their regenerative potential. Enhancing the efficacy of stem cells is critical to improve therapeutic outcomes. Dimethyl fumarate (DMF) is one of the drugs that has been recognized for its ability to modulate the paracrine effects of stem cells. This study aimed to investigate the effect of different concentrations of DMF on rat bone marrow mesenchymal stem cells (BM-MSCs). The BM-MSCs viability following treatment wit…

From Patents to Progress: Unraveling Gout's Journey Through Clinical Trials and Advancements.

Gout, an inflammatory arthritis form, is renowned for its historical association with affluence. This review delves into its pathophysiology … ed, along with promising urate-lowering drugs. Cutting-edge research on zinc ferrite nanoparticles, dimethyl fumarate, and myricetin/nobiletin hybrids addresses oxidative stress and inflammation in gout. Additionally, the potential therapeutic role of methanolic leaf extract of Euphorbia milii and tip-loaded CLC-Soluplus® MAPs is explored as natural and transdermal …