Pub Date : 2026-01-06DOI: 10.1016/j.arres.2026.100151
Changchang Zhang , Xiao Yu , Peiji Li , Xiangmei Li , Jingwen Chen , Huan Wang , Mengying Yao
Acute Respiratory Distress Syndrome (ARDS) is a serious respiratory condition characterized by a rapid onset of severe inflammation in the lungs. This inflammation results from various causes. The syndrome is marked by widespread damage to the alveolar epithelial cells and capillary endothelial cells. It represents a critical stage of acute lung injury (ALI), a prevalent clinical issue associated with a high mortality rate. The underlying mechanisms of ALI are intricate and primarily driven by an uncontrolled inflammatory response. Given this complexity, there has been growing interest recently in the role of advanced glycation end-products (AGEs) and their receptor, the receptor for advanced glycation end-products (RAGE), in the development of ALI. The AGE-RAGE signaling pathway is pivotal in the initiation and progression of ALI, influencing several processes, including inflammation and apoptosis. However, the detailed mechanisms by which this signaling pathway contributes to ALI are still being investigated. This review aims to summarize recent advancements in understanding the molecular mechanisms, regulation of inflammatory responses, and apoptosis associated with the AGE-RAGE signaling pathway in ALI. It focuses on analyzing how various traditional Chinese medicine formulas and their active components can modulate this pathway to alleviate ALI. Additionally, by integrating network pharmacology, molecular docking, and experimental validation, this review examines the interactions between the AGE-RAGE signaling pathway and significant downstream pathways such as NF-κB and PI3K/AKT, highlighting their potential therapeutic implications. Therefore, this work provides a foundational understanding of the pathogenesis of ALI and paves the way for the development of innovative therapeutic approaches.
{"title":"Targeting the AGE-RAGE axis in acute lung injury: Mechanistic insights and redox-modulatory strategies","authors":"Changchang Zhang , Xiao Yu , Peiji Li , Xiangmei Li , Jingwen Chen , Huan Wang , Mengying Yao","doi":"10.1016/j.arres.2026.100151","DOIUrl":"10.1016/j.arres.2026.100151","url":null,"abstract":"<div><div>Acute Respiratory Distress Syndrome (ARDS) is a serious respiratory condition characterized by a rapid onset of severe inflammation in the lungs. This inflammation results from various causes. The syndrome is marked by widespread damage to the alveolar epithelial cells and capillary endothelial cells. It represents a critical stage of acute lung injury (ALI), a prevalent clinical issue associated with a high mortality rate. The underlying mechanisms of ALI are intricate and primarily driven by an uncontrolled inflammatory response. Given this complexity, there has been growing interest recently in the role of advanced glycation end-products (AGEs) and their receptor, the receptor for advanced glycation end-products (RAGE), in the development of ALI. The AGE-RAGE signaling pathway is pivotal in the initiation and progression of ALI, influencing several processes, including inflammation and apoptosis. However, the detailed mechanisms by which this signaling pathway contributes to ALI are still being investigated. This review aims to summarize recent advancements in understanding the molecular mechanisms, regulation of inflammatory responses, and apoptosis associated with the AGE-RAGE signaling pathway in ALI. It focuses on analyzing how various traditional Chinese medicine formulas and their active components can modulate this pathway to alleviate ALI. Additionally, by integrating network pharmacology, molecular docking, and experimental validation, this review examines the interactions between the AGE-RAGE signaling pathway and significant downstream pathways such as NF-κB and PI3K/AKT, highlighting their potential therapeutic implications. Therefore, this work provides a foundational understanding of the pathogenesis of ALI and paves the way for the development of innovative therapeutic approaches.</div></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"18 ","pages":"Article 100151"},"PeriodicalIF":2.7,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-02DOI: 10.1016/j.arres.2026.100150
Iman Mohammadi , Behzad Einollahi , Mina Alimohammadi , Seyedeh Mahdieh Khoshnazar , Hoda Sadeghi , Ali Zahiri , Haniye Najafzadeh , Kiavash Hushmandi
Background
Chronic and acute kidney disorders (CKD, AKI) afflict millions globally, leading to increased morbidity and death, especially from cardiovascular consequences. Atorvastatin, a popular statin, offers lipid-lowering, anti-inflammatory, and antioxidant qualities that may assist kidney disease patients in terms of renal and cardiovascular health. This meta-analysis assesses atorvastatin's effectiveness and safety in terms of lipid profiles, inflammatory biomarkers, and renal function in patients with kidney disorders.
Methods
A thorough search of Scopus, Cochrane, Embase, Web of Science, Google Scholar, and PubMed until January 2025 revealed randomized controlled trials (RCTs) evaluating atorvastatin in CKD, diabetic nephropathy, hemodialysis, and other renal diseases. The outcomes included lipid parameters (HDL, LDL, total cholesterol, triglycerides), inflammatory markers (hsCRP, IL-6, MDA), and renal function indices. Random-effects models were used to pool weighted mean differences (WMDs) and 95 % confidence intervals (CIs). Subgroup analyses were performed based on dosage, duration, disease type, and treatment type. The risk of bias and publication bias was evaluated.
Results
Twelve RCTs with 18 trials and sample sizes ranging from 21 to 156 participants were included. As expected, atorvastatin significantly improved HDL cholesterol (WMD: 2.74 mg/dL; 95 % CI: 0.57 to 4.91; p < 0.001) while dramatically decreasing LDL cholesterol (WMD: -13.09 mg/dL; 95 % CI: -21.17 to -5.00; p < 0.001) and total cholesterol (WMD: -15.28 mg/dL; 95 % CI: -24.58 to -5.98; p < 0.001) at lower dosages of ≤10 mg/day and longer treatment periods. More notably, it also reduced MDA (WMD: -2.80; 95 % CI: -3.62 to -1.97; p < 0.001) and showed anti-inflammatory effects by reducing hsCRP in CKD patients receiving a ≤ 10 mg/day dosage.
Conclusions
Atorvastatin medication improves lipid profiles and lowers oxidative stress indicators in renal disease patients, with some indications of decreased inflammation in select subgroups, indicating a possible function as an adjuvant treatment to reduce cardiovascular risk. Future large-scale RCTs are needed to determine the appropriate dose and long-term kidney results.
{"title":"The effect of atorvastatin on inflammatory markers, lipid profile, and renal function in kidney diseases: a systematic review and meta-analysis of randomized controlled trials","authors":"Iman Mohammadi , Behzad Einollahi , Mina Alimohammadi , Seyedeh Mahdieh Khoshnazar , Hoda Sadeghi , Ali Zahiri , Haniye Najafzadeh , Kiavash Hushmandi","doi":"10.1016/j.arres.2026.100150","DOIUrl":"10.1016/j.arres.2026.100150","url":null,"abstract":"<div><h3>Background</h3><div>Chronic and acute kidney disorders (CKD, AKI) afflict millions globally, leading to increased morbidity and death, especially from cardiovascular consequences. Atorvastatin, a popular statin, offers lipid-lowering, anti-inflammatory, and antioxidant qualities that may assist kidney disease patients in terms of renal and cardiovascular health. This meta-analysis assesses atorvastatin's effectiveness and safety in terms of lipid profiles, inflammatory biomarkers, and renal function in patients with kidney disorders.</div></div><div><h3>Methods</h3><div>A thorough search of Scopus, Cochrane, Embase, Web of Science, Google Scholar, and PubMed until January 2025 revealed randomized controlled trials (RCTs) evaluating atorvastatin in CKD, diabetic nephropathy, hemodialysis, and other renal diseases. The outcomes included lipid parameters (HDL, LDL, total cholesterol, triglycerides), inflammatory markers (hsCRP, IL-6, MDA), and renal function indices. Random-effects models were used to pool weighted mean differences (WMDs) and 95 % confidence intervals (CIs). Subgroup analyses were performed based on dosage, duration, disease type, and treatment type. The risk of bias and publication bias was evaluated.</div></div><div><h3>Results</h3><div>Twelve RCTs with 18 trials and sample sizes ranging from 21 to 156 participants were included. As expected, atorvastatin significantly improved HDL cholesterol (WMD: 2.74 mg/dL; 95 % CI: 0.57 to 4.91; <em>p</em> < 0.001) while dramatically decreasing LDL cholesterol (WMD: -13.09 mg/dL; 95 % CI: -21.17 to -5.00; <em>p</em> < 0.001) and total cholesterol (WMD: -15.28 mg/dL; 95 % CI: -24.58 to -5.98; <em>p</em> < 0.001) at lower dosages of ≤10 mg/day and longer treatment periods. More notably, it also reduced MDA (WMD: -2.80; 95 % CI: -3.62 to -1.97; <em>p</em> < 0.001) and showed anti-inflammatory effects by reducing hsCRP in CKD patients receiving <em>a</em> ≤ 10 mg/day dosage.</div></div><div><h3>Conclusions</h3><div>Atorvastatin medication improves lipid profiles and lowers oxidative stress indicators in renal disease patients, with some indications of decreased inflammation in select subgroups, indicating a possible function as an adjuvant treatment to reduce cardiovascular risk. Future large-scale RCTs are needed to determine the appropriate dose and long-term kidney results.</div></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"18 ","pages":"Article 100150"},"PeriodicalIF":2.7,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L-carnitine is a mitochondria-targeted compound that plays a pivotal role in lipid metabolism, redox balance, and inflammatory regulation, particularly under conditions of elevated metabolic demands such as exercise. This review explores the multifaceted functions of L-carnitine in modulating oxidative stress and inflammation, emphasizing its relevance to exercise physiology and clinical health. By facilitating the transport of long-chain fatty acids into mitochondria, L-carnitine enhances β-oxidation and energy production while buffering excess acetyl-CoA to maintain metabolic flexibility. Its antioxidant properties, mediated through the upregulation of SOD, GPx, and catalase, help mitigate reactive oxygen species (ROS) and preserve mitochondrial integrity. Concurrently, L-carnitine suppresses cytokines such as TNF-α and IL-6, interrupting the feedback loop between oxidative stress and chronic inflammation. These mechanisms are particularly beneficial during and after exercise, where L-carnitine supplementation has shown potential to improve endurance, reduce muscle damage, and accelerate recovery in some studies, although findings across the literature are not entirely consistent. Clinical evidence also supports its therapeutic potential in conditions like cardiovascular disease, non-alcoholic fatty liver disease, and neuroinflammation. The review integrates mechanistic insights with performance outcomes, highlighting L-carnitine’s role as both a metabolic modulator and an ergogenic aid. Understanding these complex interactions provides a foundation for optimizing L-carnitine use, yet further research is warranted to clarify the optimal form (e.g., LCLT, ALCAR), dosage, duration, and target populations to maximize its therapeutic and ergogenic potential.
{"title":"Role of L-carnitine in exercise training: Anti-inflammatory, antioxidant, and metabolic interactions","authors":"Soheil Aminizadeh , Aliasghar Zarezadehmehrizi , Maedeh Amiri Deh-Ahmadi , Beydolah Shahouzehi","doi":"10.1016/j.arres.2025.100149","DOIUrl":"10.1016/j.arres.2025.100149","url":null,"abstract":"<div><div>L-carnitine is a mitochondria-targeted compound that plays a pivotal role in lipid metabolism, redox balance, and inflammatory regulation, particularly under conditions of elevated metabolic demands such as exercise. This review explores the multifaceted functions of L-carnitine in modulating oxidative stress and inflammation, emphasizing its relevance to exercise physiology and clinical health. By facilitating the transport of long-chain fatty acids into mitochondria, L-carnitine enhances β-oxidation and energy production while buffering excess acetyl-CoA to maintain metabolic flexibility. Its antioxidant properties, mediated through the upregulation of SOD, GPx, and catalase, help mitigate reactive oxygen species (ROS) and preserve mitochondrial integrity. Concurrently, L-carnitine suppresses cytokines such as TNF-α and IL-6, interrupting the feedback loop between oxidative stress and chronic inflammation. These mechanisms are particularly beneficial during and after exercise, where L-carnitine supplementation has shown potential to improve endurance, reduce muscle damage, and accelerate recovery in some studies, although findings across the literature are not entirely consistent. Clinical evidence also supports its therapeutic potential in conditions like cardiovascular disease, non-alcoholic fatty liver disease, and neuroinflammation. The review integrates mechanistic insights with performance outcomes, highlighting L-carnitine’s role as both a metabolic modulator and an ergogenic aid. Understanding these complex interactions provides a foundation for optimizing L-carnitine use, yet further research is warranted to clarify the optimal form (e.g., LCLT, ALCAR), dosage, duration, and target populations to maximize its therapeutic and ergogenic potential.</div></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"18 ","pages":"Article 100149"},"PeriodicalIF":2.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alkaline reduced water (ARW), produced through electrolysis, has emerged as a health-promoting beverage due to its elevated pH and reduced oxidation–reduction potential (ORP). This type of water offers several notable health benefits. ARW effectively neutralizes excess body acidity, promoting a balanced internal pH, which is beneficial in counteracting the effects of an acid-heavy diet. Its smaller molecular clusters enhance cellular absorption, improving hydration and nutrient uptake, which is particularly advantageous for athletes and physically active individuals. The antioxidant properties of ARW, attributed to its negative ORP, play a crucial role in reducing oxidative stress, thereby protecting cells from damage and potentially lowering the risk of chronic diseases such as cancer, cardiovascular diseases, and neurodegenerative disorders. ARW also supports digestive health by promoting a balanced gut environment and reducing harmful bacterial load. It also enhances the solubility and bioavailability of nutrients, improving their utilization in the body. Regular consumption of ARW has been linked to a lower incidence of chronic diseases and reduced fatigue, further enhancing energy levels. Overall ARW is a valuable addition to a health-conscious lifestyle, offering comprehensive benefits by enhancing hydration and preventing diseases. However, further research is needed to fully elucidate the long-term effects of ARW.
{"title":"A concise review on health benefits of alkaline reduced water","authors":"Maninder Meenu , Mradula , Kiran Khandare , Shradha Duggal , Vasudha Bansal , Manorma Negi , Baojun Xu","doi":"10.1016/j.arres.2025.100148","DOIUrl":"10.1016/j.arres.2025.100148","url":null,"abstract":"<div><div>Alkaline reduced water (ARW), produced through electrolysis, has emerged as a health-promoting beverage due to its elevated pH and reduced oxidation–reduction potential (ORP). This type of water offers several notable health benefits. ARW effectively neutralizes excess body acidity, promoting a balanced internal pH, which is beneficial in counteracting the effects of an acid-heavy diet. Its smaller molecular clusters enhance cellular absorption, improving hydration and nutrient uptake, which is particularly advantageous for athletes and physically active individuals. The antioxidant properties of ARW, attributed to its negative ORP, play a crucial role in reducing oxidative stress, thereby protecting cells from damage and potentially lowering the risk of chronic diseases such as cancer, cardiovascular diseases, and neurodegenerative disorders. ARW also supports digestive health by promoting a balanced gut environment and reducing harmful bacterial load. It also enhances the solubility and bioavailability of nutrients, improving their utilization in the body. Regular consumption of ARW has been linked to a lower incidence of chronic diseases and reduced fatigue, further enhancing energy levels. Overall ARW is a valuable addition to a health-conscious lifestyle, offering comprehensive benefits by enhancing hydration and preventing diseases. However, further research is needed to fully elucidate the long-term effects of ARW.</div></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"18 ","pages":"Article 100148"},"PeriodicalIF":2.7,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.1016/j.arres.2025.100147
Shiyu Liang , Youli Zhou , Wenfeng Ren , Yang Xu , Ming Tang , Yuxi Su , Li Li , Mei Gao
The Essential for Reactive Oxygen Species (EROS) protein, a critical molecular chaperone for NADPH oxidase 2 (NOX2/gp91phox), has emerged as a central regulator of redox signaling and immune defense. Recent structural and functional studies reveal that EROS orchestrates NOX2 maturation, prevents spontaneous activation, and regulates reactive oxygen species (ROS) production. Dysfunction of EROS is implicated in chronic granulomatous disease (CGD), cancers and vascular pathologies. This review integrates structural insights into EROS-NOX2 interactions, discusses its dual roles in maintaining redox equilibrium and triggering oxidative stress, and explores therapeutic strategies targeting EROS-dependent pathways.
{"title":"EROS protein: Decoding its pivotal role in redox homeostasis and disease pathogenesis","authors":"Shiyu Liang , Youli Zhou , Wenfeng Ren , Yang Xu , Ming Tang , Yuxi Su , Li Li , Mei Gao","doi":"10.1016/j.arres.2025.100147","DOIUrl":"10.1016/j.arres.2025.100147","url":null,"abstract":"<div><div>The Essential for Reactive Oxygen Species (EROS) protein, a critical molecular chaperone for NADPH oxidase 2 (NOX2/gp91<sup>phox</sup>), has emerged as a central regulator of redox signaling and immune defense. Recent structural and functional studies reveal that EROS orchestrates NOX2 maturation, prevents spontaneous activation, and regulates reactive oxygen species (ROS) production. Dysfunction of EROS is implicated in chronic granulomatous disease (CGD), cancers and vascular pathologies. This review integrates structural insights into EROS-NOX2 interactions, discusses its dual roles in maintaining redox equilibrium and triggering oxidative stress, and explores therapeutic strategies targeting EROS-dependent pathways.</div></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"18 ","pages":"Article 100147"},"PeriodicalIF":2.7,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145738770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-02DOI: 10.1016/j.arres.2025.100146
Ji ZeZhao
Methylglyoxal (MG), a core byproduct of glycolysis, exerts a dual role in cancer via a "dose-dependent hormesis effect". At low concentrations, it promotes tumor proliferation and metastasis by regulating polyamine metabolism, epigenetic modifications, and the immune microenvironment. In contrast, high concentrations of MG trigger tumor cell apoptosis through inducing DNA damage and protein glycation. Unlike traditional reviews that focus solely on "MG toxicity" or "GLO1 as a single target", this review takes "metabolic network-signal crosstalk-cross-disease association" as the core context. It systematically dissects the bidirectional regulatory mechanisms of MG in cancer, highlights emerging pathways such as non-coding RNA-mediated GLO1 regulation, MG-polyamine metabolism crosstalk, and immunometabolic reprogramming, and integrates the MG regulatory network in cross-disease scenarios including diabetes, HIV infection, and occupational exposure. Finally, a "stratified targeting + synergistic intervention" precision therapeutic strategy is proposed, providing a novel perspective for basic research and clinical translation of MG-related cancers.
{"title":"Methylglyoxal in cancer: Bidirectional regulatory networks and precision intervention—From metabolic reprogramming to cross-disease synergistic targeting","authors":"Ji ZeZhao","doi":"10.1016/j.arres.2025.100146","DOIUrl":"10.1016/j.arres.2025.100146","url":null,"abstract":"<div><div>Methylglyoxal (MG), a core byproduct of glycolysis, exerts a dual role in cancer via a \"dose-dependent hormesis effect\". At low concentrations, it promotes tumor proliferation and metastasis by regulating polyamine metabolism, epigenetic modifications, and the immune microenvironment. In contrast, high concentrations of MG trigger tumor cell apoptosis through inducing DNA damage and protein glycation. Unlike traditional reviews that focus solely on \"MG toxicity\" or \"GLO1 as a single target\", this review takes \"metabolic network-signal crosstalk-cross-disease association\" as the core context. It systematically dissects the bidirectional regulatory mechanisms of MG in cancer, highlights emerging pathways such as non-coding RNA-mediated GLO1 regulation, MG-polyamine metabolism crosstalk, and immunometabolic reprogramming, and integrates the MG regulatory network in cross-disease scenarios including diabetes, HIV infection, and occupational exposure. Finally, a \"stratified targeting + synergistic intervention\" precision therapeutic strategy is proposed, providing a novel perspective for basic research and clinical translation of MG-related cancers.</div></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"18 ","pages":"Article 100146"},"PeriodicalIF":2.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chronic inflammatory diseases (CIDs) are defined by prolonged inflammation and oxidative stress (OS), both of which are associated with disease progression and consequences. Ozone (O3) therapy is recognized as a promising complementary therapy for regulating OS indicators. The purpose of this systematic review and meta-analysis is to investigate the effect of O3 therapy on OS parameters in patients with CID.
Methods
A comprehensive literature search was conducted across multiple databases, including PubMed, Cochrane Library, Google Scholar, and Scopus, for randomized controlled trials (RCTs) published up to October 2024. Studies were selected if they investigated the effect of ozone therapy on OS parameters, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), total hydroperoxides (TH), advanced oxidation protein products (AOPP), and protein peroxidation (PP) in CID patients. Fixed- or Random-effects models were used in the meta-analysis to determine weighted mean differences (WMD) and 95 % confidence intervals (CIs).
Results
12 RCTs with 846 participants included in the current study. Our findings showed that O3 therapy had no significant difference in OS parameters when compared to control groups. According to subgroup analysis, O3 therapy significantly increased SOD activity in patients with T2D (WMD = 7.59, 95 % CI [2.98 to 12.19], I² = 97.75 %, p = <0.001) and arthritis (WMD = 9.21, 95 % CI [6.02 to 12.40], I² = 66.96 %, p = 0.08). In addition, the rectal method showed a statistically significant effect on GPx activity (WMD = 20.00, 95 % CI [0.55 to 39.45], I² = 92.42 %, p = <0.001). O3 therapy also significantly reduced AOPP levels at doses of ≥20 µg/ml and treatment durations of both <30 days (WMD = −5.15, 95 % CI [−7.90 to −2.40], I² = 96.03 %, p = <0.001).
Conclusion
Ozone therapy could improve OS markers in individuals with CIDs, mostly by lowering AOPP and strengthening antioxidant defense systems. More large-scale RCTs are required to validate these outcomes and better comprehend the fundamental mechanisms of action.
{"title":"Effect of ozone therapy on oxidative stress indices in chronic inflammatory diseases: A systematic review and meta-analysis of randomized clinical trials","authors":"Mina Alimohammadi , Seyedeh Mahdieh Khoshnazar , Hamid Khajehpour , Morteza Izadi , Behzad Einollahi , Kiavash Hushmandi","doi":"10.1016/j.arres.2025.100143","DOIUrl":"10.1016/j.arres.2025.100143","url":null,"abstract":"<div><h3>Background</h3><div>Chronic inflammatory diseases (CIDs) are defined by prolonged inflammation and oxidative stress (OS), both of which are associated with disease progression and consequences. Ozone (O<sub>3</sub>) therapy is recognized as a promising complementary therapy for regulating OS indicators. The purpose of this systematic review and meta-analysis is to investigate the effect of O<sub>3</sub> therapy on OS parameters in patients with CID.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted across multiple databases, including PubMed, Cochrane Library, Google Scholar, and Scopus, for randomized controlled trials (RCTs) published up to October 2024. Studies were selected if they investigated the effect of ozone therapy on OS parameters, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), total hydroperoxides (TH), advanced oxidation protein products (AOPP), and protein peroxidation (PP) in CID patients. Fixed- or Random-effects models were used in the meta-analysis to determine weighted mean differences (WMD) and 95 % confidence intervals (CIs).</div></div><div><h3>Results</h3><div>12 RCTs with 846 participants included in the current study. Our findings showed that O<sub>3</sub> therapy had no significant difference in OS parameters when compared to control groups. According to subgroup analysis, O<sub>3</sub> therapy significantly increased SOD activity in patients with T2D (WMD = 7.59, 95 % CI [2.98 to 12.19], I² = 97.75 %, <em>p</em> = <0.001) and arthritis (WMD = 9.21, 95 % CI [6.02 to 12.40], I² = 66.96 %, <em>p</em> = 0.08). In addition, the rectal method showed a statistically significant effect on GPx activity (WMD = 20.00, 95 % CI [0.55 to 39.45], I² = 92.42 %, <em>p</em> = <0.001). O<sub>3</sub> therapy also significantly reduced AOPP levels at doses of ≥20 µg/ml and treatment durations of both <30 days (WMD = −5.15, 95 % CI [−7.90 to −2.40], I² = 96.03 %, <em>p</em> = <0.001).</div></div><div><h3>Conclusion</h3><div>Ozone therapy could improve OS markers in individuals with CIDs, mostly by lowering AOPP and strengthening antioxidant defense systems. More large-scale RCTs are required to validate these outcomes and better comprehend the fundamental mechanisms of action.</div></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"17 ","pages":"Article 100143"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.arres.2025.100144
Zachery R. Jarrell, Ho Young Lee, Choon-Myung Lee, Michael L. Orr, Dean P. Jones, Young-Mi Go
Biological systems have evolved highly regulated systems to ensure homeostatic levels of trace minerals, such as selenium (Se), which are important to metabolic function and signaling. Much of the understanding of these systems is limited to endogenous proteins and small molecules used for trafficking of minerals. Phytochelatins, a class of plant-derived metal chelating peptides with the general structure, (γ-Glu-Cys)n-Gly, are ubiquitous in the diet and were recently found associated with Se and other metals in human urine. These findings suggest that diet-derived phytochelatins could influence metal homeostasis alongside known endogenous metal-binding compounds. In the present study, we investigated the impact of long-term, oral phytochelatin supplementation on metal homeostasis in a murine model. Phytochelatin supplementation increased Se, zinc and cobalt in the liver and increased urinary Se. Integrative analysis of liver metal profiles with untargeted, high-resolution liver metabolomics revealed dynamic metallome interaction with lipid and carbohydrate metabolism. These results highlight an active role of dietary phytochelatins in modulating mammalian metal homeostasis and associated metabolism. Such dietary components could play a pivotal role in regulating trace metal homeostasis and metal-driven pathophysiology.
{"title":"Dietary metal chelator, phytochelatin 2, increases selenium and alters metal homeostasis and associated lipid metabolism in the liver","authors":"Zachery R. Jarrell, Ho Young Lee, Choon-Myung Lee, Michael L. Orr, Dean P. Jones, Young-Mi Go","doi":"10.1016/j.arres.2025.100144","DOIUrl":"10.1016/j.arres.2025.100144","url":null,"abstract":"<div><div>Biological systems have evolved highly regulated systems to ensure homeostatic levels of trace minerals, such as selenium (Se), which are important to metabolic function and signaling. Much of the understanding of these systems is limited to endogenous proteins and small molecules used for trafficking of minerals. Phytochelatins, a class of plant-derived metal chelating peptides with the general structure, (γ-Glu-Cys)<sub>n</sub>-Gly, are ubiquitous in the diet and were recently found associated with Se and other metals in human urine. These findings suggest that diet-derived phytochelatins could influence metal homeostasis alongside known endogenous metal-binding compounds. In the present study, we investigated the impact of long-term, oral phytochelatin supplementation on metal homeostasis in a murine model. Phytochelatin supplementation increased Se, zinc and cobalt in the liver and increased urinary Se. Integrative analysis of liver metal profiles with untargeted, high-resolution liver metabolomics revealed dynamic metallome interaction with lipid and carbohydrate metabolism. These results highlight an active role of dietary phytochelatins in modulating mammalian metal homeostasis and associated metabolism. Such dietary components could play a pivotal role in regulating trace metal homeostasis and metal-driven pathophysiology.</div></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"17 ","pages":"Article 100144"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.arres.2025.100142
Nazmun Nahar , Md. Shihab Uddin Sohag
Mitochondria, a crucial subcellular organelle, serve as the primary generator of reactive oxygen species (producing around 90 % of total ROS), utilizing over 98 % of cellular oxygen for ATP synthesis while converting 1–2 % into ROS. Excess reactive oxygen species disrupt redox homeostasis, inducing oxidative stress, resulting in mitochondrial dysfunction and damage. Furthermore, defective or impaired mitochondria might intensify ROS production. This "necessary evil" serves dual functions: regulating signaling, apoptosis, proliferation, differentiation, autophagy, and immunological responses while simultaneously inflicting oxidative damage on lipids, proteins, and DNA, hence contributing to numerous diseases. Thus, the targeted suppression of mitochondrial ROS-induced oxidative damage and dysfunction by mitochondria-targeted antioxidants (MTAs) represents a precise therapeutic strategy that has attracted growing interest and offers substantial opportunities for clinical application by directly alleviating oxidative stress at its origin within affected cells. Lipophilic cation-linked MTAs, amino acid- and peptide-based MTAs, metallo-complex-based MTAs, and nanoparticle-based MTAs (Nano-MTAs) can selectively localize to mitochondria and diminish excessive mitochondrial ROS. Incorporating these MTAs into precision medicine facilitates tailored therapies based on individual mitochondrial dysfunction characteristics and disease-specific redox imbalances. This review classifies current mitochondria-targeted antioxidants according to the characteristics of their targeting moieties and examines their composition and antioxidant efficacy. We also evaluate nanoparticle-based MTAs, including liposomes, DQAsomes, solid lipid nanoparticles, MITO-Porters, micelles, dendrimers, nanoemulsions, metal nanoparticles, quantum dots, and nanopolyplexes. Furthermore, we summarize recent experimental findings regarding MTAs across diverse disease models including cancer, neurological disorders (e.g., Alzheimer’s, Huntington’s, Parkinson’s, ataxia, TBI, and epilepsy); cardiovascular diseases; asthma; COPD; auditory impairments; diabetic complications; ocular, renal, hepatic, and inflammatory disorders; sepsis; infertility; aging-longevity; and their potential as antibiotics to clarify the evidence supporting their therapeutic efficacy.
{"title":"Advancements in mitochondrial-targeted antioxidants: Organelle-specific drug delivery for disease management","authors":"Nazmun Nahar , Md. Shihab Uddin Sohag","doi":"10.1016/j.arres.2025.100142","DOIUrl":"10.1016/j.arres.2025.100142","url":null,"abstract":"<div><div>Mitochondria, a crucial subcellular organelle, serve as the primary generator of reactive oxygen species (producing around 90 % of total ROS), utilizing over 98 % of cellular oxygen for ATP synthesis while converting 1–2 % into ROS. Excess reactive oxygen species disrupt redox homeostasis, inducing oxidative stress, resulting in mitochondrial dysfunction and damage. Furthermore, defective or impaired mitochondria might intensify ROS production. This \"necessary evil\" serves dual functions: regulating signaling, apoptosis, proliferation, differentiation, autophagy, and immunological responses while simultaneously inflicting oxidative damage on lipids, proteins, and DNA, hence contributing to numerous diseases. Thus, the targeted suppression of mitochondrial ROS-induced oxidative damage and dysfunction by mitochondria-targeted antioxidants (MTAs) represents a precise therapeutic strategy that has attracted growing interest and offers substantial opportunities for clinical application by directly alleviating oxidative stress at its origin within affected cells. Lipophilic cation-linked MTAs, amino acid- and peptide-based MTAs, metallo-complex-based MTAs, and nanoparticle-based MTAs (Nano-MTAs) can selectively localize to mitochondria and diminish excessive mitochondrial ROS. Incorporating these MTAs into precision medicine facilitates tailored therapies based on individual mitochondrial dysfunction characteristics and disease-specific redox imbalances. This review classifies current mitochondria-targeted antioxidants according to the characteristics of their targeting moieties and examines their composition and antioxidant efficacy. We also evaluate nanoparticle-based MTAs, including liposomes, DQAsomes, solid lipid nanoparticles, MITO-Porters, micelles, dendrimers, nanoemulsions, metal nanoparticles, quantum dots, and nanopolyplexes. Furthermore, we summarize recent experimental findings regarding MTAs across diverse disease models including cancer, neurological disorders (e.g., Alzheimer’s, Huntington’s, Parkinson’s, ataxia, TBI, and epilepsy); cardiovascular diseases; asthma; COPD; auditory impairments; diabetic complications; ocular, renal, hepatic, and inflammatory disorders; sepsis; infertility; aging-longevity; and their potential as antibiotics to clarify the evidence supporting their therapeutic efficacy.</div></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"17 ","pages":"Article 100142"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1016/j.arres.2025.100145
Ahmed Abdulrazzaq Bapir , Burhan Ahmed Salih , Goran Othman
Background
Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by chronic hyperglycemia, oxidative stress, and low-grade inflammation. The CYP8B1 gene, a key regulator of bile acid synthesis and hepatic metabolism, may be influenced by oxidative status and has emerged as a potential contributor to T2DM pathogenesis. This study examined the association between CYP8B1 rs3732860 polymorphism, gene expression levels, and various biochemical and oxidative stress markers in individuals with T2DM.
Methods
A total of 198 subjects (132 T2DM patients and 66 healthy controls) were genotyped for the CYP8B1 rs3732860 variant. Biochemical parameters including HbA1c, glutathione peroxidase (GPX), catalase, malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-10 (IL-10), interferon-gamma (IFN-γ), and nitric oxide (NO) were measured. CYP8B1 expression was assessed using qPCR (ΔCt values). Statistical analyses included logistic regression, chi-square, ANOVA, and ROC curve analysis.
Results
The TC genotype was significantly associated with increased T2DM risk (OR = 4.51, 95 % CI: 1.85–11.01, p = 0.001), while the CC genotype showed a non-significant trend (OR = 2.25, p = 0.078). CYP8B1 expression differed significantly among genotypes (p < 0.001), with highest expression in CC carriers. MDA levels also varied by genotype (p = 0.001), suggesting a link between oxidative stress and gene regulation. ROC analysis identified catalase (AUC = 0.909) and SOD (AUC = 0.764) as strong predictors of T2DM.
Conclusion
The CYP8B1 rs3732860 polymorphism is associated with altered gene expression and oxidative stress in T2DM, highlighting its potential role as a metabolic regulator and biomarker of disease susceptibility.
{"title":"Association of CYP8B1 rs3732860 polymorphism and gene expression with oxidative stress and biochemical markers in Type 2 diabetes mellitus","authors":"Ahmed Abdulrazzaq Bapir , Burhan Ahmed Salih , Goran Othman","doi":"10.1016/j.arres.2025.100145","DOIUrl":"10.1016/j.arres.2025.100145","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by chronic hyperglycemia, oxidative stress, and low-grade inflammation. The CYP8B1 gene, a key regulator of bile acid synthesis and hepatic metabolism, may be influenced by oxidative status and has emerged as a potential contributor to T2DM pathogenesis. This study examined the association between CYP8B1 rs3732860 polymorphism, gene expression levels, and various biochemical and oxidative stress markers in individuals with T2DM.</div></div><div><h3>Methods</h3><div>A total of 198 subjects (132 T2DM patients and 66 healthy controls) were genotyped for the CYP8B1 rs3732860 variant. Biochemical parameters including HbA1c, glutathione peroxidase (GPX), catalase, malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-10 (IL-10), interferon-gamma (IFN-γ), and nitric oxide (NO) were measured. CYP8B1 expression was assessed using qPCR (ΔCt values). Statistical analyses included logistic regression, chi-square, ANOVA, and ROC curve analysis.</div></div><div><h3>Results</h3><div>The TC genotype was significantly associated with increased T2DM risk (OR = 4.51, 95 % CI: 1.85–11.01, <em>p</em> = 0.001), while the CC genotype showed a non-significant trend (OR = 2.25, <em>p</em> = 0.078). CYP8B1 expression differed significantly among genotypes (<em>p</em> < 0.001), with highest expression in CC carriers. MDA levels also varied by genotype (<em>p</em> = 0.001), suggesting a link between oxidative stress and gene regulation. ROC analysis identified catalase (AUC = 0.909) and SOD (AUC = 0.764) as strong predictors of T2DM.</div></div><div><h3>Conclusion</h3><div>The CYP8B1 rs3732860 polymorphism is associated with altered gene expression and oxidative stress in T2DM, highlighting its potential role as a metabolic regulator and biomarker of disease susceptibility.</div></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"18 ","pages":"Article 100145"},"PeriodicalIF":2.7,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145694906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}