Standard of care versus new-wave corticosteroids in the treatment of Duchenne muscular dystrophy: Can we do better?

Orphanet Journal of Rare Diseases, Journal Year: 2021, Volume and Issue: 16(1)

Published: March 4, 2021

Abstract Background Pharmacological corticosteroid therapy is the standard of care in Duchenne Muscular Dystrophy (DMD) that aims to control symptoms and slow disease progression through potent anti-inflammatory action. However, a major concern significant adverse effects associated with long term-use. Main This review discusses pros cons treatment for DMD compares it novel data generated new-wave dissociative corticosteroid, vamorolone. The current status experimental pharmaceuticals also reviewed, insights regarding alternative drugs could provide therapeutic advantage. Conclusions Although steroids may be superior substitutes corticosteroids, other potential therapeutics should explored. Repurposing or developing pharmacological therapies capable addressing many pathogenic features addition anti-inflammation elicit greater advantages.

Language: Английский

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Resveratrol Alleviates Zearalenone-Induced Intestinal Dysfunction in Mice through the NF-κB/Nrf2/HO-1 Signalling Pathway

Foods, Journal Year: 2024, Volume and Issue: 13(8), P. 1217 - 1217

Published: April 17, 2024

Zearalenone (ZEA), a mycotoxin widely present in crops and food, poses major threat to animal human health. The consumption of ZEA-contaminated food or feed causes intestinal damage. Therefore, exploring how mitigate the damage caused by its ZEA is becoming increasingly important. Resveratrol (RSV), polyphenol compound, mainly exists Vitis vinifera, Polygonum cuspidatum, Arachis hypogaea, other plants. It has potent anti-inflammatory antioxidant activity. primary objective this study was assess defensive effects RSV molecular mechanism on mucosal injury induced exposure mice. results showed that pretreatment significantly reduced serum DAO D-lactate levels altered morphology markedly restored TJ protein levels, goblet cell number, MUC-2 gene expression after challenge. In addition, reversed pro-inflammatory factor abnormal changes MDA, CAT, T-SOD. Additional research demonstrated decreased inflammation blocking translocation nuclear factor-kappaB (NF-κB) p65 oxidative stress activating E2-related 2 (Nrf2) pathway associated genes, including NQO1, γ-GCS, GSH-PX. summary, supplementation attenuates stress, inflammation, barrier dysfunction mediating NF-κB Nrf2/HO-1 pathways.

Language: Английский

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Ferulic acid and hormesis: Biomedical and environmental implications

Mechanisms of Ageing and Development, Journal Year: 2021, Volume and Issue: 198, P. 111544 - 111544

Published: July 15, 2021

Language: Английский

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Mitochondria and Reactive Oxygen Species: The Therapeutic Balance of Powers for Duchenne Muscular Dystrophy

Cells, Journal Year: 2024, Volume and Issue: 13(7), P. 574 - 574

Published: March 26, 2024

Duchenne muscular dystrophy (DMD) is a genetic progressive muscle-wasting disorder that leads to rapid loss of mobility and premature death. The absence functional dystrophin in DMD patients reduces sarcolemma stiffness increases contraction damage, triggering cascade events leading muscle cell degeneration, chronic inflammation, deposition fibrotic adipose tissue. Efforts the last decade have led clinical approval novel drugs for aim restore function. However, combination therapies able expression target myriad cellular found impaired dystrophic are desirable. Muscles higher energy consumers susceptible mitochondrial defects. Mitochondria generate significant source reactive oxygen species (ROS), they are, turn, sensitive proper redox balance. In both animal models there compelling evidence impairments key role failure homeostasis. Here, we highlighted main aspects dysfunction oxidative stress discussed recent findings linked mitochondria/ROS-targeted molecules as therapeutic approach. this respect, dual targeting mitochondria homeostasis emerges potential option DMD.

Language: Английский

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Saccharomyces boulardii Ameliorates Dextran Sulfate Sodium‐Induced Ulcerative Colitis in Mice by Regulating NF‐κB and Nrf2 Signaling Pathways

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Saccharomyces boulardii ( S. ) is a probiotic yeast that widely used to treat gastrointestinal disorders. The present study aimed explore the therapeutic effects of on dextran sulfate sodium‐ (DSS‐) induced murine ulcerative colitis (UC) and illustrate mechanisms action. C57BL/6 mice were administered (10 5 10 7 CFU/ml, p.o. for 3 weeks then given DSS [2.5% w / v )] one week. Administration prevented DSS‐induced reduction in body weight, diarrhea, bloody feces, decreased colon length, loss histological structure. Moreover, protected intestinal barrier by increasing levels tight junction proteins zona occludens‐1 Occludin exerted immunomodulatory mice. Furthermore, suppressed colonic inflammation reducing Interleukin‐1 β , Interleukin‐6, Tumor necrosis factor alpha restored myeloperoxidase activity exposed DSS. also mitigated oxidative damage antioxidant enzymes (superoxide dismutase, catalase, heme oxygenase 1) glutathione decreasing malondialdehyde accumulation. Further studies identified nuclear translocation kappa B (NF‐ κ B) p65 subunit I K α levels, while promoted erythroid 2‐related 2 (Nrf2) DSS‐exposed Collectively, possessed an appreciable effect against experimental model UC. protective mechanism may involve inhibition NF‐ B‐mediated proinflammatory signaling activation Nrf2‐modulated defense addition effects.

Language: Английский

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Nuclear Factor Erythroid-2-Related Factor 2 Signaling in the Neuropathophysiology of Inherited Metabolic Disorders

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Nov. 26, 2021

Inherited metabolic disorders (IMDs) are rare genetic conditions that affect multiple organs, predominantly the central nervous system. Since treatment for a large number of IMDs is limited, there an urgent need to find novel therapeutical targets. Nuclear factor erythroid-2-related 2 (Nrf2) transcription has key role in controlling intracellular redox environment by regulating expression antioxidant enzymes and several important genes related homeostasis. Considering oxidative stress along with system alterations mechanism involved neuropathophysiology many IMDs, this review focuses on current knowledge about Nrf2 signaling dysregulation observed group characterized neurological dysfunction. We here X-linked adrenoleukodystrophy, glutaric acidemia type I, hyperhomocysteinemia, Friedreich’s ataxia. Additionally, beneficial effects different activators shown, identifying promising target patients these disorders. expect article stimulates research into investigation pathway involvement use potential pharmacological modulators counteract exert neuroprotection.

Language: Английский

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Redox Homeostasis in Muscular Dystrophies

Cells, Journal Year: 2021, Volume and Issue: 10(6), P. 1364 - 1364

Published: June 1, 2021

In recent years, growing evidence has suggested a prominent role of oxidative stress in the pathophysiology several early- and adult-onset muscle disorders, although effective antioxidant treatments are still lacking. Oxidative causes cell damage by affecting protein function, membrane structure, lipid metabolism, DNA integrity, thus interfering with skeletal homeostasis functionality. Some features related to stress, such as chronic inflammation, defective regeneration, mitochondrial shared among most muscular dystrophies, Nrf2 been shown be central player antagonizing redox imbalance these disorders. However, exact mechanisms leading overproduction reactive oxygen species deregulation cellular antioxidants system seem be, large extent, disease-specific, clarification vivo humans is cornerstone for development targeted therapies, which will require testing appropriately designed clinical trials.

Language: Английский

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Homeostasis and evolution in relation to regeneration and repair

The Journal of Physiology, Journal Year: 2024, Volume and Issue: 602(11), P. 2627 - 2648

Published: May 23, 2024

Homeostasis constitutes a key concept in physiology and refers to self-regulating processes that maintain internal stability when adjusting changing external conditions. It diminishes entropy constituting driving force behind evolution. Natural selection might act on homeostatic regulatory mechanisms control including homeodynamics, allostasis, hormesis homeorhesis, where different stable stationary states are reached. Regeneration is under through hormesis. Damage tissues initiates response restore the impaired equilibrium caused by mild stress using cell proliferation, differentiation death recover structure function. Repair homeorhetic change leading new state with decreased functionality fibrotic scarring without reconstruction of 3-D pattern. Mechanisms determining entrance tissue or organ regeneration repair include balance between innate adaptive immune cells relation plasticity stromal stem responses, redox balance. The regenerative reparative capacities vary species, distinct organs, at stages development ageing. Many signals pathways play crucial roles regulating protein synthesis, cellular growth, inflammation, autophagy, lysosomal function, metabolism metalloproteinase signalling. Attempts favour damaged those low proliferative rates have been made; however, there evolutionary constraint poor proliferation unfavourable environments tumour development. More research required better understand these mechanisms.

Language: Английский

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Oral administration of plumbagin is beneficial in in vivo models of Duchenne muscular dystrophy through control of redox signaling

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 225, P. 193 - 207

Published: Sept. 24, 2024

Language: Английский

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Calming the (Cytokine) Storm: Dimethyl Fumarate as a Therapeutic Candidate for COVID-19

Pharmaceuticals, Journal Year: 2020, Volume and Issue: 14(1), P. 15 - 15

Published: Dec. 26, 2020

COVID-19 has rapidly spread worldwide and incidences of hospitalisation from respiratory distress are significant. While a vaccine is in the pipeline, there urgency for therapeutic options to address immune dysregulation, hyperinflammation oxidative stress that can lead death. Given shared pathogenesis severe cases with aspects multiple sclerosis psoriasis, we propose dimethyl fumarate as viable treatment option. Currently approved an immunomodulatory, anti-inflammatory anti-oxidative drug could be implemented into clinic calm cytokine storm which drives COVID-19.

Language: Английский

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