Special Issue "Antioxidants and Oxidative Stress in the Development of Diseases and Therapy"

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: 31 January 2024 | Viewed by 4426

Special Issue Editors

Academy of Medical Science, School of Basic Medical Science, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou University, Zhengzhou, 450008, China
Interests: cancer development; cancer therapeutic resistance; carcinogenesis; angiogenesis
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Prof. Dr. Canhua Huang
E-Mail Website
Guest Editor
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
Interests: redox regulation in tumorigenesis; the mechanism of virus-induced tumorigenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Oxidative stress is the imbalance of reactive oxygen species (ROS) and endogenous antioxidants, and is the driving cause of many human diseases, including neurodegenerative diseases, cancer, cardiovascular diseases, immune-system disorders, and musculoskeletal diseases. The dramatically increased human lifespan leads to the increased prevalence of these oxidative-stress-related diseases, which may be prevented and treated in order to reduce an economic and psychological burden for patients, their families and society that is currently showing a progressive increase. Healthy aging is crucial and needs to be highlighted as it affects the quality of lifespan. Recent evidence shows that antioxidants and small molecules for inhibiting ROS have therapeutic potential in preclinical studies and clinical trials. A better understanding of mechanisms of ROS production and antioxidant action is important for disease prevention and treatment in the future.

Oxidative stress induces cell proliferation, cellular senescence, and/or cell death through multiple mechanisms, including mitochondrial dysfunction, mitophagy impairment, apoptosis, protein modification, non-coding RNA dysregulation, and other epigenetic regulations. In the past few years, translational research has been extensively carried to elucidate the molecular mechanisms of oxidative stress and to find new chemicals or naturally derived compounds and antioxidants for the treatment of these oxidative-stress-related diseases.

This Special Issue will focus on the molecular mechanisms of oxidative stress in causing major human diseases, as well as the therapeutic and nutraceutical effects and molecular mechanisms of antioxidants, both naturally and synthetically derived, on oxidative-stress-induced diseases. It is our hope that this Special Issue will review molecular mechanisms of oxidative stress and redox signaling in disease development, and that it will advance our understanding of translational and clinical studies using antioxidants to foster new strategies for disease prevention.

Prof. Dr. Binghua Jiang
Prof. Dr. Canhua Huang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • human disease
  • cancer
  • neurodegenerative diseases
  • age-related diseases
  • antioxidants
  • oxidative stress
  • reactive oxygen species
  • cell senescence
  • non-coding RNAs
  • epigenetic regulations

Published Papers (4 papers)

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Research

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Article
Integrated Multi-Omics Analysis for Inferring Molecular Players in Inclusion Body Myositis
Antioxidants 2023, 12(8), 1639; https://doi.org/10.3390/antiox12081639 - 19 Aug 2023
Viewed by 446
Abstract
Inclusion body myositis (IBM) is an acquired inflammatory myopathy affecting proximal and distal muscles that leads to weakness in patients over 50. It is diagnosed based on clinical and histological findings in muscle related to inflammation, degeneration, and mitochondria. In relation to IBM, [...] Read more.
Inclusion body myositis (IBM) is an acquired inflammatory myopathy affecting proximal and distal muscles that leads to weakness in patients over 50. It is diagnosed based on clinical and histological findings in muscle related to inflammation, degeneration, and mitochondria. In relation to IBM, a shortage of validated disease models and a lack of biomarkers and effective treatments constitute an unmet medical need. To overcome these hurdles, we performed an omics analysis of multiple samples from IBM patients (saliva, fibroblasts, urine, plasma, and muscle) to gain insight into the pathophysiology of IBM. Degeneration was evident due to the presence of amyloid β peptide 1–42 (Aβ1–42) in the saliva of the analyzed IBM patients. The presence of metabolic disarrangements in IBM was indicated by an imbalanced organic acid profile in fibroblasts and urine. Specifically, abnormal levels of L-pyroglutamic and orotic acid were supported by the abnormal expression of related metabolites in plasma and urine (glutathione and pyrimidines) and the aberrant expression of upstream gene regulators (L2HGDH, IDH2, OPLAH, and ASL) in muscle. Combined levels of L-pyroglutamic and orotic acid displayed an outstanding biomarker signature in urine with 100% sensitivity and specificity. The confirmation of systemic metabolic disarrangements in IBM and the identification of novel biomarkers reported herein unveil novel insights that require validation in larger cohorts. Full article
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Article
CRISPR/Cas9-Based Screening of FDA-Approved Drugs for NRF2 Activation: A Novel Approach to Discover Therapeutics for Non-Alcoholic Fatty Liver Disease
Antioxidants 2023, 12(7), 1363; https://doi.org/10.3390/antiox12071363 - 29 Jun 2023
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Abstract
With the rising prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) now affects 20–25% of the global population. NAFLD, a progressive condition associated with oxidative stress, can result in cirrhosis and liver cancer in 10% and 3% of patients suffering NAFLD, respectively. Therapeutic [...] Read more.
With the rising prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) now affects 20–25% of the global population. NAFLD, a progressive condition associated with oxidative stress, can result in cirrhosis and liver cancer in 10% and 3% of patients suffering NAFLD, respectively. Therapeutic options are currently limited, emphasizing the need for novel treatments. In this study, we examined the potential of activating the transcription factor NRF2, a crucial player in combating oxidative stress, as an innovative approach to treating NAFLD. Utilizing a CRISPR/Cas9-engineered human HEK293T cell line, we were able to monitor the expression of heme oxygenase-1 (HMOX1), an NRF2 target, using a Nanoluc luciferase tag. Our model was validated using a known NRF2 activator, after which we screened 1200 FDA-approved drugs, unearthing six compounds (Disulfiram, Thiostrepton, Auranofin, Thimerosal, Halofantrine, and Vorinostat) that enhanced NRF2 activity and antioxidant response. These compounds demonstrated protective effects against oxidative stress induced by hydrogen peroxide and lipid droplets accumulation in vitro with hepatoma HUH-7 cells. Our study underscores the utility of CRISPR/Cas9 tagging with Nanoluc luciferase in identifying potential NRF2 activators, paving the way for potential NAFLD therapeutics. Full article
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Article
The Xanthine Oxidase Inhibitor Febuxostat Suppresses Adipogenesis and Activates Nrf2
Antioxidants 2023, 12(1), 133; https://doi.org/10.3390/antiox12010133 - 05 Jan 2023
Cited by 2 | Viewed by 1619
Abstract
Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine catabolism that acts as a novel regulator of adipogenesis. In pathological states, xanthine oxidoreductase activity increases to produce excess reactive oxygen species (ROS). The nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical [...] Read more.
Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine catabolism that acts as a novel regulator of adipogenesis. In pathological states, xanthine oxidoreductase activity increases to produce excess reactive oxygen species (ROS). The nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical inducer of antioxidants, which is bound and repressed by a kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm. The Keap1-Nrf2 axis appears to be a major mechanism for robust inducible antioxidant defenses. Here, we demonstrate that febuxostat, a xanthine oxidase inhibitor, alleviates the increase in adipose tissue mass in obese mouse models with a high-fat diet or ovariectomy. Febuxostat disrupts in vitro adipocytic differentiation in adipogenic media. Adipocytes appeared at day 7 in absence or presence of febuxostat were 160.8 ± 21.2 vs. 52.5 ± 12.7 (p < 0.01) in 3T3–L1 cells, and 126.0 ± 18.7 vs. 55.3 ± 13.4 (p < 0.01) in 10T1/2 cells, respectively. Adipocyte differentiation was further enhanced by the addition of hydrogen peroxide, which was also suppressed by febuxostat. Interestingly, febuxostat, but not allopurinol (another xanthine oxidase inhibitor), rapidly induced the nuclear translocation of Nrf2 and facilitated the degradation of Keap1, similar to the electrophilic Nrf2 activator omaveloxolone. These results suggest that febuxostat alleviates adipogenesis under oxidative conditions, at least in part by suppressing ROS production and Nrf2 activation. Regulation of adipocytic differentiation by febuxostat is expected to inhibit obesity due to menopause or overeating. Full article
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Review

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Review
Advances in the Use of N-Acetylcysteine in Chronic Respiratory Diseases
Antioxidants 2023, 12(9), 1713; https://doi.org/10.3390/antiox12091713 - 02 Sep 2023
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Abstract
N-acetylcysteine (NAC) is widely used because of its mucolytic effects, taking part in the therapeutic protocols of cystic fibrosis. NAC is also administered as an antidote in acetaminophen (paracetamol) overdosing. Thanks to its wide antioxidative and anti-inflammatory effects, NAC may also be [...] Read more.
N-acetylcysteine (NAC) is widely used because of its mucolytic effects, taking part in the therapeutic protocols of cystic fibrosis. NAC is also administered as an antidote in acetaminophen (paracetamol) overdosing. Thanks to its wide antioxidative and anti-inflammatory effects, NAC may also be of benefit in other chronic inflammatory and fibrotizing respiratory diseases, such as chronic obstructive pulmonary disease, bronchial asthma, idiopathic lung fibrosis, or lung silicosis. In addition, NAC exerts low toxicity and rare adverse effects even in combination with other treatments, and it is cheap and easily accessible. This article brings a review of information on the mechanisms of inflammation and oxidative stress in selected chronic respiratory diseases and discusses the use of NAC in these disorders. Full article
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