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Organ-specific autoimmune diseases
Published in Gabriel Virella, Medical Immunology, 2019
Gabriel Virella, George C. Tsokos
Recently, several new pharmacological agents have been found to be useful in the treatment of MS. Teriflunomide, a pyrimidine synthesis inhibitor, has been found in phase III trials to be equivalent to IFNβ. Dimethyl fumarate has a comparable clinical effect that correlates inversely with lymphocyte counts and has been approved by the U.S. Food and Drug Administration (FDA). Fingolimod, a sphingosine-1-phosphate-1 receptor antagonist, inhibits the egression of lymphocytes from lymph nodes to the bloodstream. It has been shown to have a good clinical effect and has also been approved by the FDA. Natalizumab is a humanized monoclonal antibody that recognizes the adhesion molecule α4 integrin and blocks its interaction with the vascular cell adhesion molecule 1. Natalizumab has great clinical efficacy. A downside is there is a substantial risk for the development of progressive multifocal leukoencephalopathy caused by activation of the JC virus. Other monoclonal antibodies shown to be clinically valuable and used to treat MS are the B cell–depleting antibodies (rituximab and ocrelizumab).
Current and future oral small molecules
Published in M. Alan Menter, Caitriona Ryan, Psoriasis, 2017
Peter Weisenseel, Kristian Reich
The clinical efficacy of oral dimethyl fumarate (DMF) in the treatment of MS has been demonstrated in two pivotal phase III studies. Dimethyl fumarate reduced relapse rates by about 50% compared with placebo.11 Reduction in disability progression was significant in only one of the two studies. The formulation and dosing of FAEs for MS differ from Fumaderm. The approved dosing of dimethyl fumarate for MS is 240 mg, two or three times per day (SmPC Tecfidera).
Isoliquiritin modulates ferroptosis via NF-κB signaling inhibition and alleviates doxorubicin resistance in breast cancer
Published in Immunopharmacology and Immunotoxicology, 2023
Jiguo Wang, Yang Li, Jing Zhang, Changguo Luo
NF-κB signaling pathway plays an important role in the development, inflammation, and immunity of breast cancer [45]. In addition, the NF-κB signaling pathway is also involved in the regulation of ferroptosis, oxidative stress, glycolysis, and inflammation. Dimethyl fumarate improves ferroptosis, oxidative stress, and inflammation to ameliorate cognitive deficits involved in the NF-κB signaling axis [46]. Betulinic acid inhibits aerobic glycolysis related to the NF-κB pathway in breast cancer [47]. Furthermore, Li et al. [18] reveal that Iso alleviates depression associated with the NF-κB pathway. The anti-oxidative stress and anti-inflammation effects of Iso on the membranous glomerulonephritis model are also involved in the NF-κB signaling pathway [32]. Here, our results exhibited that Iso treatment notably counteracted the LPS-induced relative protein levels of p-p50/p50, p-p65/p65, and IκB both in vitro and in vivo. Also, Iso introduction significantly reversed the LPS-induced changes in the levels of ferroptosis, oxidative stress, glycolysis, and inflammation. Together with these findings, Iso mediated the oxidative stress, glycolysis, and inflammation through ferroptosis involved in the NF-κB signaling pathways in breast cancer.
Immunosuppressive effects of dimethyl fumarate on dendritic cell maturation and migration: a potent protector for coronary heart disease
Published in Immunopharmacology and Immunotoxicology, 2022
Zikai Sun, Xiaoqiang Liu, Yu Liu, Xin Zhao, Xuan Zang, Fang Wang
Dimethyl fumarate (DMF), an agent which consists of a combination of fumaric acid esters, has been shown to exert anti-oxidative and anti-inflammatory properties in many tissues, such as the nervous system, liver, and heart [15–17]. Recently, DMF has been shown to have a significant protective effect against ischemia/reperfusion (I/R) injury in both the brain and liver [18,19]. DMF has also shown cardioprotective effects by activating the Nrf2 antioxidant-signaling pathway [20], however, the principal mechanism for the cardioprotective effects of DMF remains poorly understood. As previously mentioned, targeting DC functions may be an effective approach to treating atherosclerotic disease. Thus, we investigated whether one of the mechanisms critical for the cardioprotective effects of DMF is related to the regulation of DC functions. In this study, we investigated the effects of DMF on the functions of DCs treated with lipopolysaccharide (LPS) and serum obtained from patients with acute myocardial infarction (AMI).
Cost per PASI-75 responder of calcipotriol plus betamethasone dipropionate cutaneous foam versus nonbiologic systemic therapies for the treatment of plaque psoriasis in seven European countries
Published in Journal of Dermatological Treatment, 2021
Deepak M. W. Balak, Jose-Manuel Carrascosa, Stamatis Gregoriou, Piergiacomo Calzavara-Pinton, Anthony Bewley, Joana Antunes, Martin E. Nyeland, Marta G. Viola, Laura M. Sawyer, Lidia Becla
The consumption of methotrexate could not be derived from the observational study synthesized in the MAIC (13), so was calculated based on the label posology (14) and a titration period validated by clinical experts. Patients were assumed to start on 7.5 mg of methotrexate per week and escalate to 10 mg in weeks 2 and 3, to 15 mg in weeks 4 to 6, to 20 mg in weeks 7 to 10 and to 25 mg in weeks 11 and 12. This amounts to an average weekly dose of 16.9 mg for the first 12 weeks. The dose of acitretin is determined by patient weight and was derived from Chiricozzi et al. (15), the observational study synthesized in the MAIC. The mean dosage in this study was 25.01 mg (SD ± 6.79) corresponding to a mean of 0.31 mg/kg. Multiplied by the mean patient weight from the PSO-ABLE study (87 kg), the mean daily dosage was 27 mg. The dose of apremilast was 30 mg twice daily following a 5-day titration. Dimethyl fumarate was given at a daily dose of 240 mg three times daily after a nine-week titration schedule.