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Review, Journal: NINJ1: A new player in multiple sclerosis pathogenesis and potential therapeutic target. (Pubmed Central) - Sep 17, 2024 Finally, the review examines potential therapeutic strategies targeting NINJ1 for improved MS management. Abbreviations: MS, Multiple sclerosis; CNS, Central nervous system; BBB, Blood-brain barrier; GSDMD, Gasdermin-D; EAE, Experimental autoimmune encephalitis; HMGB-1, High mobility group box-1 protein; LDH, Lactate dehydrogenase; PMR, Plasma membrane rupture; DMF, Dimethyl fumarate; DUSP1, Dual-specificity phosphatase 1; PAMPs, Pathogen-associated molecular patterns; DAMPs, Danger-associated molecular patterns; PRRs, Pattern recognition receptors; GM-CSF, Granulocyte-macrophage colony stimulating factor; IFN-?, Interferon gamma; TNF, Tumor necrosis factor; APCs, Antigen-presenting cells; ECs, Endothelial cells; TGF-?, Transforming growth factor-?; PBMCs, Peripheral blood mononuclear cells; FACS, Fluorescence-activated cell sorting; MCP-1, Monocyte chemoattractant protein-1; NLRP3, Pyrin domain-containing 3; TCR, T cell receptor; ROS, Reactive oxygen species; AP-1, Activator protein-1; ANG1, Angiopoietin 1; BMDMs, Bone marrow-derived macrophages; Arp2/3, actin-related protein 2/3; EMT, epithelial-mesenchymal transition; FAK, focal adhesion kinase; LIMK1, LIM domain kinase 1; PAK1, p21-activated kinases 1; Rac1, Ras-related C3 botulinum toxin substrate 1; ?-cat, ?-caten; MyD88, myeloid differentiation primary response gene 88; TIRAP, Toll/interleukin-1 receptor domain-containing adapter protein; TLR4, Toll-like receptor 4; IRAKs, interleukin-1 receptor-associated kinases; TRAF6, TNF receptor associated factor 6; TAB2/3, TAK1 binding protein 2/3; TAK1, transforming growth factor-?-activated kinase 1; JNK, c-Jun N-terminal kinase; ERK1/2, Extracellular Signal Regulated Kinase 1/2; IKK, inhibitor of kappa B kinase; I?B, inhibitor of NF-?B; NF-?B, nuclear factor kappa-B; AP-1, activator protein-1; ASC, Apoptosis-associated Speck-like protein containing a CARD; NEK7, NIMA-related kinase 7; NLRP3, Pyrin domain-containing 3; CREB, cAMP response element-binding protein.
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Preclinical, Journal: Dimethyl Fumarate-Loaded Gellan Gum Hydrogels Can Reduce In Vitro Chemokine Expression in Oral Cells. (Pubmed Central) - Sep 14, 2024 In support of our strategy, DMF-enriched gellan gum hydrogels significantly reduced the forced chemokine expression in gingival fibroblasts. Our data suggest that DMF exerts its anti-inflammatory activity in periodontal cells when released from gellan gum hydrogels, suggesting a potential clinical relevance to control overshooting chemokine expression under chronic inflammatory conditions.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab, Mavenclad (cladribine) / EMD Serono, Lemtrada (alemtuzumab) / Sanofi
Clinical, Retrospective data, Review, Journal, Immunomodulating: Immunomodulators and immunosuppressants for progressive multiple sclerosis: a network meta-analysis. (Pubmed Central) - Sep 10, 2024 Given the relative rarity of PMS, controlled, non-randomised studies on large samples may usefully integrate data from pivotal RCTs. Outcomes valuable and meaningful to people with PMS should be consistently adopted and measured to permit the evaluation of relative effectiveness among treatments.
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IL-17/IL-17R-axis: a novel airway signaling pathway in cystic fibrosis? () - Sep 4, 2024 - Abstract #NACFC2024NACFC_922; Outcomes valuable and meaningful to people with PMS should be consistently adopted and measured to permit the evaluation of relative effectiveness among treatments. Our in vitro studies suggest that, in addition to IL-17A, IL-17B, IL-17C, IL-17E, IL-17F, and their receptors may play a role in CF pathophysiology.
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Biomarker, Preclinical, Journal, PD(L)-1 Biomarker, IO biomarker: Evaluation of S (Pubmed Central) - Sep 2, 2024 Interestingly, a repeated analysis after 3 months of treatment revealed the CTCL cell death sensitivity to be restored by therapy. We propose this novel integrated approach comprising the evaluation of SC marker expression and analysis of cell death sensitivity upon treatment that can also enable a better therapy stratification.
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Journal: Nrf2/FSP1/CoQ10 axis-mediated ferroptosis is involved in sodium aescinate-induced nephrotoxicity. (Pubmed Central) - Aug 19, 2024 Overexpression of Nrf2 or its agonist dimethyl fumarate (DMF) promoted FSP1 expression, thereby improving cellular antioxidant capacity and alleviating SA-induced ferroptosis. These results suggest that SA-triggers renal injury through oxidative stress and ferroptosis, driven by the suppression of the Nrf2/FSP1/CoQ10 axis.
- |||||||||| dimethyl fumarate / Generic mfg., disulfiram / Generic mfg.
Journal: Gain-of-function variants in GSDME cause pyroptosis and apoptosis associated with post-lingual hearing loss. (Pubmed Central) - Aug 6, 2024 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 potential treatment strategies.
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Journal: "PTSD symptoms among patients with multiple sclerosis in Jordan during October 7th gaza war outbreak". (Pubmed Central) - Aug 6, 2024 In conclusion, this study elucidated the molecular mechanism associated with hearing loss caused by GSDME gene mutations, offering novel insights for potential treatment strategies. The high rate of significant PTSD symptoms among people with MS in this study underscores the need for attention by primary care providers and implementation of a comprehensive multidisciplinary approach to optimize the mental well-being of this fragile population.
- |||||||||| Tysabri (natalizumab) / Biogen, Royalty
Journal, Immune cell: Implications of disease-modifying therapies for multiple sclerosis on immune cells and response to COVID-19 vaccination. (Pubmed Central) - Jul 30, 2024 Here, we evaluated the immune cell effects of 3 DMTs on the response to mRNA SARS-CoV-2 vaccination by comparing MS patients treated with one specific therapy (fingolimod, dimethyl fumarate, or natalizumab) with both healthy controls and untreated patients...Also, anti-spike specific B cells progressively increased over the three time points after vaccination, even when antibodies measured from the same samples instead showed a decline. Our findings demonstrate that repeated booster vaccinations in MS patients are crucial to overcoming the immune cell impairment caused by DMTs and achieving an immune response to the SARS-CoV-2 vaccine comparable to that of healthy controls.
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Macrophage polarization by monomethyl fumarate as a therapeutic target treatment in osteoarthritis (Exhibition Hall/Poster Area) - Jul 18, 2024 - Abstract #IASP2024IASP_1439; Our studies with the EOA model induced by MIA suggest a new perspective for human treatment committed with OA based on macrophage polarization as a therapeutic target, switching the pro-inflammatory profile M1 to the anti-inflammatory profile M2 with MMF local treatment. However, more studies are fully required to understand the MMF treatment and the role of macrophage (M2) to promote cartilage repair and reduce pain signals.
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Preclinical, Journal: Low-dose dimethylfumarate attenuates colitis-associated cancer in mice through M2 macrophage polarization and blocking oxidative stress. (Pubmed Central) - Jul 11, 2024 Current chemotherapy for CAC, based on 5-fluorouracil and oxalipltin, is not fully effective and displays severe side effects, prompting the search for alternative therapies...Low-dose (DMF30) and high-dose of DMF (DMF100) or oxaliplatin (OXA) were administered from the 8th to 12th week of the experiment, and then the colon tissues were analysed histologically and biochemically...DMF had a dual effect on CAC. At low dose, DMF is chemotherapeutic and acts as an antioxidant and immunomodulator, whereas at high dose, DMF is pro-oxidant and exacerbates colitis-associated cancer.
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Journal: Dimethyl Fumarate-Associated Enterocolitis. (Pubmed Central) - Jul 8, 2024 The benefit of disease-modifying therapy in RIS may extend to CNS structures impacted by neurodegeneration that is below the resolution of conventional volumetric measures. No abstract available
- |||||||||| Skyclarys (omaveloxolone) / Biogen, Vincerinone (vatiquinone) / Sumitomo Pharma, PTC Therap
Review, Journal: The Role of NRF2 in Trinucleotide Repeat Expansion Disorders. (Pubmed Central) - Jun 27, 2024 However, translating these findings into successful clinical applications requires further research. In this article, we review the literature supporting the role of NRF2 in the pathogenesis of these diseases and the potential therapeutics of NRF2 activators.
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