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Dimethylfumarate

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https://www.readbyqxmd.com/read/28633807/differential-induction-of-atf3-and-ho-1-in-myeloid-cells-and-keratinocytes-via-dimethylfumarate-or-cyclosporine-a
#1
Stefanie Müller, Nikola Smatlik, Marc Burian, Kamran Ghoreschi, Martin Röcken, Amir S Yazdi
BACKGROUND: Chronic inflammatory skin diseases are characterized by controlled proliferation of keratinocytes. Here, activating transcription factor 3 (ATF3) might play a fundamental role. In these inflammatory diseases, proliferation is controlled and only rarely leads to cancer development which can be supported by an inflammatory microenvironment. ATF3 is a dual function protein as it suppresses pro-inflammatory IL-6 and IL-8, but also acts as a pro-oncogenic factor by the suppression of p53...
June 12, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28526975/lipid-nanoparticles-for-administration-of-poorly-water-soluble-neuroactive-drugs
#2
Elisabetta Esposito, Markus Drechsler, Paolo Mariani, Federica Carducci, Michela Servadio, Francesca Melancia, Patrizia Ratano, Patrizia Campolongo, Viviana Trezza, Rita Cortesi, Claudio Nastruzzi
This study describes the potential of solid lipid nanoparticles and nanostructured lipid carriers as nano-formulations to administer to the central nervous system poorly water soluble drugs. Different neuroactive drugs, i.e. dimethylfumarate, retinyl palmitate, progesterone and the endocannabinoid hydrolysis inhibitor URB597 have been studied. Lipid nanoparticles constituted of tristearin or tristearin in association with gliceryl monoolein were produced. The nanoencapsulation strategy allowed to obtain biocompatible and non-toxic vehicles, able to increase the solubility of the considered neuroactive drugs...
September 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28486503/depletion-of-saccharomyces-cerevisiae-in-psoriasis-patients-restored-by-dimethylfumarate-therapy-dmf
#3
Hester Eppinga, H Bing Thio, Marco W J Schreurs, Blerdi Blakaj, Ruena I Tahitu, Sergey R Konstantinov, Maikel P Peppelenbosch, Gwenny M Fuhler
BACKGROUND: Psoriasis and inflammatory bowel disease (IBD) are chronic inflammatory diseases sharing similar pathogenic pathways. Intestinal microbial changes such as a decrease of bakers' yeast Saccharomyces cerevisiae have been reported in IBD, suggesting the presence of a gut-skin axis. OBJECTIVE: To investigate whether the S. cerevisiae abundance was altered in psoriasis patients versus healthy controls, and whether dimethylfumarate (DMF) interacted with this yeast...
2017: PloS One
https://www.readbyqxmd.com/read/28322482/progressive-multifocal-leukoencephalopathy-associated-with-fumaric-acid-esters-treatment-in-psoriasis-patients
#4
Deepak M W Balak, Enes Hajdarbegovic, Wichor M Bramer, Martino H A Neumann, H Bing Thio
BACKGROUND: Fumaric acid esters (FAEs) are a systemic treatment for psoriasis considered to have a favorable long-term safety profile without an increased risk for immunosuppression. However, progressive multifocal leukoencephalopathy (PML), a rare, opportunistic viral infection of the central nervous system, has been linked anecdotally to FAE treatment. OBJECTIVE: to assess clinical features and outcomes of FAE-associated PML cases. METHODS: Systematic literature search in multiple databases up to February, 25(th) 2016 for reports of PML in psoriasis patients treated with FAEs...
March 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28123399/the-status-of-nrf2-based-therapeutics-current-perspectives-and-future-prospects
#5
REVIEW
Irina G Gazaryan, Bobby Thomas
This mini-review presents the authors' vision on the current status and future trends in the development of neuroprotective agents working via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), and in particular, via disruption of Nrf2-Keap1 interaction. There are two opposite "chemical" mechanisms underlying such activation: the first one is a non-specific covalent modification of Keap1 thiols, resulting in side effects of varied severity, and the second one is the shift of the Nrf2-Kelch-like ECH associated protein-1 (Keap1) binding equilibrium in the presence of a competitive and chemically benign displacement agent...
November 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27743338/erratum-to-dimethylfumarate-induces-cell-cycle-arrest-and-apoptosis-via-regulating-intracellular-redox-systems-in-hela-cells
#6
Guocan Han, Qiang Zhou
No abstract text is available yet for this article.
December 2016: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/27496192/dimethylfumarate-induces-cell-cycle-arrest-and-apoptosis-via-regulating-intracellular-redox-systems-in-hela-cells
#7
Guocan Han, Qiang Zhou
Dimethylfumarate (DMF) is cytotoxic to several kinds of cells and serves as an anti-tumor drug. This study was designed to investigate the effects and underlying mechanism of DMF on cervical cancer cells. HeLa cells were cultured and treated with 0, 50, 100, 150, and 200 μM DMF, respectively. After 24 h, cell growth was evaluated using Cell Counting Kit-8 (CCK-8) assay and the cell cycle was examined using flow cytometry. In addition, cell apoptosis was detected by Annexin V/propidium iodide (PI) staining and the expressions of caspase-3 and poly-ADP-ribose polymerase (PARP) were detected using western blotting...
December 2016: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/27468725/dimethylfumarate-inhibits-melanoma-cell-proliferation-via-p21-and-p53-induction-and-bcl-2-and-cyclin-b1-downregulation
#8
Irina Kaluzki, Igor Hrgovic, Tsige Hailemariam-Jahn, Monika Doll, Johannes Kleemann, Eva Maria Valesky, Stefan Kippenberger, Roland Kaufmann, Nadja Zoeller, Markus Meissner
Recent evidence suggests that dimethylfumarate (DMF), known as a highly potent anti-psoriatic agent, might have anti-tumorigenic properties in melanoma. It has recently been demonstrated that DMF inhibits melanoma proliferation by apoptosis and cell cycle inhibition and therefore inhibits melanoma metastasis. Nonetheless, the underlying mechanisms remain to be evaluated. To elucidate the effects of DMF on melanoma cell lines (A375, SK-Mel), we first performed cytotoxicity assays. No significant lactatedehydogenase (LDH) release could be found...
October 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27376248/dimethyl-and-monomethylfumarate-regulate-indoleamine-2-3-dioxygenase-ido-activity-in-human-immune-cells
#9
Sevgi Eminel, Na Jin, Martin Rostami, Stefan Dibbert, Ulrich Mrowietz, Ina Suhrkamp
Fumaric acid esters (FAEs) are used as an oral treatment for psoriasis. Dimethylfumarate (DMF) and its metabolite monomethylfumarate (MMF) are regarded as the pharmacologically active moieties. Indoleamine 2,3-dioxygenase (IDO) is the key enzyme for the metabolism of tryptophan. The kynurenine pathway is established as a major regulator of innate and adaptive immunity. Here, we investigated the effect of DMF and MMF on IDO activity and expression in human peripheral blood mononuclear cells (PBMCs). IDO activity was determined by measuring the concentration of kynurenine in the culture medium using a HPLC technique...
July 4, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27312167/immunological-treatment-of-multiple-sclerosis
#10
Martin Diebold, Tobias Derfuss
Treatment of multiple sclerosis (MS) has been a challenge since its first description by Charcot. The advent of immunomodulatory drugs in the mid 1990s brought the first big change in the treatment of MS patients. During the last 10 years there has been an ongoing tremendous evolution of novel treatment options for relapsing-remitting MS. These options include monoclonal antibodies, which inhibit migration of lymphocytes (natalizumab), deplete lymphocytes (alemtuzumab), or block the cytokine receptor interleukin (IL)-2 (daclizumab), teriflunomide that inhibits proliferation of activated lymphocytes, fingolimod that modulates the sphingosine-receptor system, and dimethylfumarate that combines features of immunomodulatory and immunosuppressive drugs...
April 2016: Seminars in Hematology
https://www.readbyqxmd.com/read/27277809/distinct-nrf2-signaling-mechanisms-of-fumaric-acid-esters-and-their-role-in-neuroprotection-against-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-induced-experimental-parkinson-s-like-disease
#11
Manuj Ahuja, Navneet Ammal Kaidery, Lichuan Yang, Noel Calingasan, Natalya Smirnova, Arsen Gaisin, Irina N Gaisina, Irina Gazaryan, Dmitry M Hushpulian, Ismail Kaddour-Djebbar, Wendy B Bollag, John C Morgan, Rajiv R Ratan, Anatoly A Starkov, M Flint Beal, Bobby Thomas
UNLABELLED: A promising approach to neurotherapeutics involves activating the nuclear-factor-E2-related factor 2 (Nrf2)/antioxidant response element signaling, which regulates expression of antioxidant, anti-inflammatory, and cytoprotective genes. Tecfidera, a putative Nrf2 activator, is an oral formulation of dimethylfumarate (DMF) used to treat multiple sclerosis. We compared the effects of DMF and its bioactive metabolite monomethylfumarate (MMF) on Nrf2 signaling and their ability to block 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental Parkinson's disease (PD)...
June 8, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27192495/the-keap1-nrf2-are-pathway-as-a-potential-preventive-and-therapeutic-target-an-update
#12
REVIEW
Meng-Chen Lu, Jian-Ai Ji, Zheng-Yu Jiang, Qi-Dong You
The Keap1-Nrf2-ARE ((Kelch-like ECH-Associating protein 1) nuclear factor erythroid 2 related factor 2-antioxidant response element) pathway is one of the most important defense mechanisms against oxidative and/or electrophilic stresses, and it is closely associated with inflammatory diseases, including cancer, neurodegenerative diseases, cardiovascular diseases, and aging. In recent years, progress has been made in strategies aimed at modulating the Keap1-Nrf2-ARE pathway. The Nrf2 activator DMF (Dimethylfumarates) has been approved by the FDA as a new first-line oral drug to treat patients with relapsing forms of multiple sclerosis, while a phase 3 study of another promising candidate, CDDO-Me, was terminated for safety reasons...
September 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27105770/severe-recalcitrant-cutaneous-manifestations-in-systemic-lupus-erythematosus-successfully-treated-with-fumaric-acid-esters
#13
A M Saracino, C H Orteu
Fumaric acid esters (FAEs) have proven efficacy in the treatment of psoriasis and have been in use for decades. More recently, as their mechanism of action and abundant immunomodulatory effects become clearer, the potential benefits of treating other inflammatory skin conditions using FAEs are increasingly being recognized. The use of FAEs as combination systemic therapy has not been well studied and data are lacking regarding the safety and efficacy of this type of therapy. In this case report, three patients with severe, extensive and recalcitrant cutaneous manifestations of systemic lupus erythematosus (SLE) (one case of disseminated discoid lesions and two with severe chilblain lesions) were treated with Fumaderm(®) (containing the FAE dimethylfumarate and monoethylhydrogen fumarate salts), after failing to respond to a multitude of other monotherapies and combination therapies...
February 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/26946710/-pharmacovigilance-update
#14
Kim Dao, Haithem Chtioui, Laura E Rothuizen, Léonore Diezi, Sylvain Prod'hom, Ursula Winterfeld, Thierry Buclin, Françoise Livio
The main pharmacovigilance updates in 2015are reviewed. Sofosbuvir amiodarone interaction: risk of severe bradycardia. Dasabuvir clopidogrel interaction: increased dasabuvir concentrations and potential risk of QTprolongation. SGLT2 inhibitors: risks of diabetic acidocetosis and bone fracture. Dabigatran: therapeutic drug monitoring may improve benefit-risk ratio. Ibuprofen: at higher dosage, vascular risks are comparable to coxibs. Pregabaline, gabapentine: potential for abuse and addiction. Varenicline: potentiates alcohol's effects...
January 13, 2016: Revue Médicale Suisse
https://www.readbyqxmd.com/read/26921765/attenuation-of-7-ketocholesterol-induced-overproduction-of-reactive-oxygen-species-apoptosis-and-autophagy-by-dimethyl-fumarate-on-158n-murine-oligodendrocytes
#15
Amira Zarrouk, Thomas Nury, El-Mostafa Karym, Anne Vejux, Randa Sghaier, Catherine Gondcaille, Pierre Andreoletti, Doriane Trompier, Stéphane Savary, Mustapha Cherkaoui-Malki, Meryam Debbabi, Agnès Fromont, Jean-Marc Riedinger, Thibault Moreau, Gérard Lizard
Mitochondrial dysfunctions and oxidative stress are involved in several non demyelinating or demyelinating neurodegenerative diseases. Some of them, including multiple sclerosis (MS), are associated with lipid peroxidation processes leading to increased levels of 7-ketocholesterol (7KC). So, the eventual protective effect of dimethylfumarate (DMF), which is used for the treatment of MS, was evaluated on 7KC-treated oligodendrocytes, which are myelin synthesizing cells. To this end, murine oligodendrocytes 158N were exposed to 7KC (25, 50μM) for 24h without or with DMF (1, 25, 50μM)...
May 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/26903865/different-contribution-of-redox-sensitive-transient-receptor-potential-channels-to-acetaminophen-induced-death-of-human-hepatoma-cell-line
#16
Heba Badr, Daisuke Kozai, Reiko Sakaguchi, Tomohiro Numata, Yasuo Mori
Acetaminophen (APAP) is a safe analgesic antipyretic drug at prescribed doses. Its overdose, however, can cause life-threatening liver damage. Though, involvement of oxidative stress is widely acknowledged in APAP-induced hepatocellular death, the mechanism of this increased oxidative stress and the associated alterations in Ca(2+) homeostasis are still unclear. Among members of transient receptor potential (TRP) channels activated in response to oxidative stress, we here identify that redox-sensitive TRPV1, TRPC1, TRPM2, and TRPM7 channels underlie Ca(2+) entry and downstream cellular damages induced by APAP in human hepatoma (HepG2) cells...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/26831413/multiple-sclerosis-new-treatment-modalities
#17
REVIEW
Rocco Totaro, Caterina Di Carmine, Carmine Marini, Antonio Carolei
Ever since the introduction of the first disease modifying therapies, the concept of multiple sclerosis treatment algorithms developed ceaselessly. The increasing number of available drugs is paralleled by impelling issue of ensuring the most appropriate treatment to the right patient at the right time. The purpose of this review is to describe novel agents recently approved for multiple sclerosis treatment, namely teriflunomide, alemtuzumab and dimethylfumarate, focusing on mechanism of action, efficacy data in experimental setting, safety and tolerability...
December 2015: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/26763431/dimethylfumarate-impairs-neutrophil-functions
#18
COMPARATIVE STUDY
Susen Müller, Martina Behnen, Katja Bieber, Sonja Möller, Lars Hellberg, Mareike Witte, Martin Hänsel, Detlef Zillikens, Werner Solbach, Tamás Laskay, Ralf J Ludwig
Host defense against pathogens relies on neutrophil activation. Inadequate neutrophil activation is often associated with chronic inflammatory diseases. Neutrophils also constitute a significant portion of infiltrating cells in chronic inflammatory diseases, for example, psoriasis and multiple sclerosis. Fumarates improve the latter diseases, which so far has been attributed to the effects on lymphocytes and dendritic cells. Here, we focused on the effects of dimethylfumarate (DMF) on neutrophils. In vitro, DMF inhibited neutrophil activation, including changes in surface marker expression, reactive oxygen species production, formation of neutrophil extracellular traps, and migration...
January 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/26690241/dimethyl-fumarate-reduces-inflammatory-responses-in-experimental-colitis
#19
Giovanna Casili, Marika Cordaro, Daniela Impellizzeri, Giuseppe Bruschetta, Irene Paterniti, Salvatore Cuzzocrea, Emanuela Esposito
BACKGROUND AND AIMS: Fumaric acid esters have been proven to be effective for the systemic treatment of psoriasis and multiple sclerosis. We aimed to develop a new treatment for colitis. METHODS: We investigated the effect of dimethylfumarate [DMF, 10-30-100mg/kg] on an experimental model of colitis induced by dinitrobenzene sulphuric acid [DNBS]. We also evaluated the therapeutic activity of 7 weeks' treatment with DMF [30mg/kg] on 9-week-old IL-10KO mice that spontaneously develop a T helper-1 [Th1]-dependent chronic enterocolitis after birth, that is fully established at 8-10 weeks of age...
April 2016: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/26663097/dimethylfumarate-effectively-inhibits-lymphangiogenesis-via-p21-induction-and-g1-cell-cycle-arrest
#20
Eva Maria Valesky, Igor Hrgovic, Monika Doll, Xiao-Fan Wang, Andreas Pinter, Johannes Kleemann, Roland Kaufmann, Stefan Kippenberger, Markus Meissner
Different pathologies, such as lymphoedema, cancer or psoriasis, are associated with abnormal lymphatic vessel formation. Therefore, influencing lymphangiogenesis is an interesting target. Recent evidence suggests that dimethylfumarate (DMF), an antipsoriatic agent, might have antitumorigenic and antilymphangiogenic properties. To prove this assumption, we performed proliferation and functional assays with primary human dermal lymphendothelial cells (DLEC). We could demonstrated that DMF suppresses DLEC proliferation and formation of capillary-like structures...
March 2016: Experimental Dermatology
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