Oxidative Medicine and Cellular Longevity最新文献

[This corrects the article DOI: 10.1155/2018/1874985.].

[This corrects the article DOI: 10.1155/2022/4295208.].

Oxidative stress, driven by an imbalance between oxidants and antioxidants, disrupts redox homeostasis and contributes to the development of chronic diseases, including cancer, diabetes, neurodegenerative disorders, and aging. The NRF2-KEAP1 pathway is a pivotal cellular defense mechanism against oxidative stress, regulating the transcription of cytoprotective genes. Pharmacological NRF2 activation has emerged as a promising strategy to mitigate oxidative stress-related pathologies; however, challenges regarding target specificity, pharmacodynamics, efficacy, and safety remain unresolved. Isoeugenol, a phenylpropanoid found in essential oils, has traditionally been recognized as a skin allergen but is now gaining attention for its potential as an NRF2 activator. Emerging evidence suggests that isoeugenol exerts antioxidant, anti-inflammatory, and neuroprotective effects and modulates metabolic disorders such as diabetes mellitus. Despite its therapeutic potential, the direct correlation between isoeugenol's effects and NRF2 activation remains underexplored. Existing studies indicate that isoeugenol may activate NRF2 through multiple mechanisms, including covalent modification of KEAP1 cysteine residues, increased AKT activation and GSK3β inactivation, and glutathione depletion leading to reactive oxygen species (ROS) generation. Understanding these activation pathways is critical for leveraging isoeugenol as a therapeutic agent. This review provides a comprehensive analysis of isoeugenol's role in modulating NRF2 activity and its implications for treating oxidative stress-driven diseases. By integrating current findings, this review highlights new insights into the therapeutic potential of isoeugenol in translational medicine. We propose future research directions to optimize its application in clinical settings, paving the way for more targeted and effective NRF2-based interventions in chronic disease management.

Increased levels of glutathione (GSH) and related antioxidant processes are thought to predict breast tumor aggressiveness and therapy response. In our 2012 review of 21 studies, we found that most patient breast tumors exhibited increased GSH levels compared to peritumoral tissue. However, there was no clear relationship between GSH levels and histological grade, clinical stage, or patient outcome. For this update, database searches found 59 studies that reported the levels of any of 10 metabolites, including GSH, cysteine (Cys), ascorbate (Asc), and taurine (Tau), in breast tumor tissues. The increase in the number of studies profiling tumor metabolites is mainly due to the use of an array of relatively new metabolomics technologies. However, many of these metabolomics methods are not designed to prevent sample oxidation during tissue procurement and processing. Despite this, these recent studies confirm that the levels of most of the antioxidants or related metabolites are increased in patient breast tumor tissues compared to normal tissues. In addition, poor patient outcomes are often associated with tumor tissues with higher GSH and lower Tau levels. GSH levels also increase with histological grade. There are no clear trends in the relationship between any of the antioxidant levels and tumor stage or genetically defined subtypes. Clearer trends may emerge with more uniform tissue sampling, preparation, and assay procedures. In addition, the increased use of spatial metabolomics methods may help to clarify the relationship between antioxidant levels and clinical markers.

[This corrects the article DOI: 10.1155/2019/5972575.].

[This retracts the article DOI: 10.1155/2021/3672112.].

[This retracts the article DOI: 10.1155/2017/1206420.].

Background: Oxidative stress plays a crucial role in the pathogenesis of preeclampsia. Given that the NADPH quinone oxidoreductase 1 (NQO1) is an important enzyme in the antioxidant system, this study aimed to investigate the relationship between the NQO1 rs1800566 polymorphism, NQO1 promoter methylation, and oxidative stress with the risk of preeclampsia.

Methods: This case-control study analyzed 170 women, including preeclampsia patients and healthy pregnant women. To investigate the NQO1 rs1800566 variants, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used. Promoter methylation analysis in 96 of these samples was conducted using quantitative methylation-specific PCR (qMSP) method. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity, along with zinc (Zn), copper (Cu), selenium (Se), malondialdehyde (MDA), and total antioxidant capacity (TAC) levels were measured using chemical methods.

Results: We found reduced levels of TAC, Zn, and Se, and also the SOD activity in patients than controls. However, the MDA and Cu levels, and the GPx activity increased in preeclamptic patients. No association was identified between the NQO1 rs1800566 variants or NQO1 promoter methylation with the risk of preeclampsia.

Conclusion: It seems the NQO1 rs1800566 and the promoter methylation of NQO1 gene are not involved in the risk of preeclampsia. However, our findings indicate the presence of oxidative stress in preeclamptic patients.

Obesity-associated metabolic dysfunction is closely linked to chronic low-grade inflammation, or metaflammation, which is predominantly driven by changes in AT homeostasis. Macrophages, key components of the innate immune system, are central regulators of this inflammatory process. In lean AT, resident macrophages (AT-associated macrophages [ATMs]) exhibit an anti-inflammatory phenotype and support tissue homeostasis. However, during obesity, AT undergoes hypoxia, mechanical stress, and lipid overload, leading to immune cell infiltration and a phenotypic switch of ATMs toward a proinflammatory M1 profile. This shift contributes to systemic inflammation and obesity-associated metabolic risks. Here, we review the current understanding of macrophage polarization in obesity, highlighting the transcriptomic plasticity and functional heterogeneity of ATMs, their interactions within the AT microenvironment, and the formation of crown-like structures (CLSs) as a structural hallmark of AT inflammation. We also discuss the regulatory functions of transcription factors, such as hypoxia-inducible factor (HIF) 1α (HIF-1α) and peroxisome proliferator activated receptor gamma (PPARγ), that control the phenotypic switch of macrophages in healthy and obese ATs. Furthermore, we examined emerging macrophage subsets, such as CD9⁺ and Trem2⁺ lipid-associated macrophages (LAMs), and their dual roles in AT remodeling and inflammation. Understanding the complex network of macrophage activation in obese AT is essential for identifying therapeutic targets aimed at mitigating obesity-associated metabolic risk and restoring tissue function.

[This retracts the article DOI: 10.1155/2020/8026838.].