The p53/NF-kappaB-dependent induction of sestrin2 by amyloid-beta peptides exerts antioxidative actions in neurons
Free Radic Biol Med. 2021 Apr 11:S0891-5849(21)00206-9. doi: 10.1016/j.freeradbiomed.2021.04.004. Online ahead of print.ABSTRACTAccumulation of senile plaques mainly composed of neurotoxic amyloid-beta peptide (Aβ) is a pathological hallmark of Alzheimer's disease (AD). Sestrin2 inducible by various types of stressors is known to promote autophagy and exert antioxidative effects. In this work, we revealed the molecular mechanisms underlying Aβ induction of sestrin2 and tested whether antioxidation, in addition to autophagy regulation, also contributes to its neuroprotective effects in primary rat cortical neurons...
Source: Free Radical Biology and Medicine - April 14, 2021 Category: Biology Authors: Yi-Heng Hsieh A-Ching Chao Yi-Chun Lin Shang-Der Chen Ding-I Yang Source Type: research

Editorial: "Mitochondrial Coenzyme Q Homeostasis: signalling, respiratory chain stability and diseases."
Free Radic Biol Med. 2021 Apr 9:S0891-5849(21)00207-0. doi: 10.1016/j.freeradbiomed.2021.04.005. Online ahead of print.NO ABSTRACTPMID:33845159 | DOI:10.1016/j.freeradbiomed.2021.04.005 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 12, 2021 Category: Biology Authors: Placido Navas Alberto Sanz Source Type: research

Editorial: "Mitochondrial Coenzyme Q Homeostasis: signalling, respiratory chain stability and diseases."
Free Radic Biol Med. 2021 Apr 9:S0891-5849(21)00207-0. doi: 10.1016/j.freeradbiomed.2021.04.005. Online ahead of print.NO ABSTRACTPMID:33845159 | DOI:10.1016/j.freeradbiomed.2021.04.005 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 12, 2021 Category: Biology Authors: Placido Navas Alberto Sanz Source Type: research

Prolyl Oligopeptidase Inhibition Reduces Oxidative Stress via Reducing NADPH Oxidase Activity by Activating Protein Phosphatase 2A
In conclusion, our results suggest that PREP inhibition could also provide neuroprotection by reducing OS, thus broadening the scope of its beneficial effects on neurodegeneration.PMID:33838285 | DOI:10.1016/j.freeradbiomed.2021.04.001 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 10, 2021 Category: Biology Authors: T Etel äinen V Kulmala R Svarcbahs M J äntti T T My öhänen Source Type: research

Changes in redox plasma proteome of Pon1-/- mice are exacerbated by a hyperhomocysteinemic diet
Free Radic Biol Med. 2021 Apr 7:S0891-5849(21)00202-1. doi: 10.1016/j.freeradbiomed.2021.03.042. Online ahead of print.ABSTRACTHigh-density lipoprotein (HDL), in addition to promoting reverse cholesterol transport, possesses anti-oxidative, anti-inflammatory, and antithrombotic activities, which are thought to be promoted by paraoxonase 1 (PON1), an HDL-associated enzyme. Reduced levels of PON1 are associated with increased oxidative stress and cardiovascular disease both in humans and Pon1-/- mice. However, molecular basis of these associations are not fully understood. We used label-free mass spectrometry and Ingenuity P...
Source: Free Radical Biology and Medicine - April 10, 2021 Category: Biology Authors: Marta Sikora Hieronim Jakubowski Source Type: research

Prolyl Oligopeptidase Inhibition Reduces Oxidative Stress via Reducing NADPH Oxidase Activity by Activating Protein Phosphatase 2A
In conclusion, our results suggest that PREP inhibition could also provide neuroprotection by reducing OS, thus broadening the scope of its beneficial effects on neurodegeneration.PMID:33838285 | DOI:10.1016/j.freeradbiomed.2021.04.001 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 10, 2021 Category: Biology Authors: T Etel äinen V Kulmala R Svarcbahs M J äntti T T My öhänen Source Type: research

Changes in redox plasma proteome of Pon1-/- mice are exacerbated by a hyperhomocysteinemic diet
Free Radic Biol Med. 2021 Apr 7:S0891-5849(21)00202-1. doi: 10.1016/j.freeradbiomed.2021.03.042. Online ahead of print.ABSTRACTHigh-density lipoprotein (HDL), in addition to promoting reverse cholesterol transport, possesses anti-oxidative, anti-inflammatory, and antithrombotic activities, which are thought to be promoted by paraoxonase 1 (PON1), an HDL-associated enzyme. Reduced levels of PON1 are associated with increased oxidative stress and cardiovascular disease both in humans and Pon1-/- mice. However, molecular basis of these associations are not fully understood. We used label-free mass spectrometry and Ingenuity P...
Source: Free Radical Biology and Medicine - April 10, 2021 Category: Biology Authors: Marta Sikora Hieronim Jakubowski Source Type: research

Prolyl Oligopeptidase Inhibition Reduces Oxidative Stress via Reducing NADPH Oxidase Activity by Activating Protein Phosphatase 2A
In conclusion, our results suggest that PREP inhibition could also provide neuroprotection by reducing OS, thus broadening the scope of its beneficial effects on neurodegeneration.PMID:33838285 | DOI:10.1016/j.freeradbiomed.2021.04.001 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 10, 2021 Category: Biology Authors: T Etel äinen V Kulmala R Svarcbahs M J äntti T T My öhänen Source Type: research

Changes in redox plasma proteome of Pon1-/- mice are exacerbated by a hyperhomocysteinemic diet
Free Radic Biol Med. 2021 Apr 7:S0891-5849(21)00202-1. doi: 10.1016/j.freeradbiomed.2021.03.042. Online ahead of print.ABSTRACTHigh-density lipoprotein (HDL), in addition to promoting reverse cholesterol transport, possesses anti-oxidative, anti-inflammatory, and antithrombotic activities, which are thought to be promoted by paraoxonase 1 (PON1), an HDL-associated enzyme. Reduced levels of PON1 are associated with increased oxidative stress and cardiovascular disease both in humans and Pon1-/- mice. However, molecular basis of these associations are not fully understood. We used label-free mass spectrometry and Ingenuity P...
Source: Free Radical Biology and Medicine - April 10, 2021 Category: Biology Authors: Marta Sikora Hieronim Jakubowski Source Type: research

Dioscin ameliorates methotrexate-induced liver and kidney damages via adjusting miRNA-145-5p-mediated oxidative stress
Free Radic Biol Med. 2021 Apr 6:S0891-5849(21)00195-7. doi: 10.1016/j.freeradbiomed.2021.03.035. Online ahead of print.ABSTRACTDioscin, one natural product, has various pharmacological actions. However, its effects on methotrexate (MTX)-induced hepatorenal damages still remain unknown. In the present study, the data manifested that dioscin restored the viabilities of L-02 and NRK-52E cells, reduced ALT, AST, Cr, BUN levels, and ameliorated histopathological changes of liver and kidney. Besides, dioscin decreased ROS levels in cells, and adjusted SOD, MDA, GSH and GSH-Px levels in rats. Dioscin reduced the expression levels...
Source: Free Radical Biology and Medicine - April 9, 2021 Category: Biology Authors: Y Li M Gao L-H Yin L-N Xu Y Qi Pengyuan Sun J-Y Peng Source Type: research

Elemental iron modifies the redox environment of the gastrointestinal tract: a novel therapeutic target and test for metabolic syndrome
Free Radic Biol Med. 2021 Apr 5:S0891-5849(21)00192-1. doi: 10.1016/j.freeradbiomed.2021.03.032. Online ahead of print.ABSTRACTMetabolic syndrome (MetS, i.e., type 2 diabetes and obesity) is often associated with dysbiosis, inflammation, and leaky gut syndrome, which increase the content of oxygen and reactive oxygen species (ROS) in the gastrointestinal (GI) tract. Using near-infrared fluorescent, in situ imaging of ROS, we evaluated the effects of oral administration of elemental iron powder (Fe0) on luminal ROS in the GI tract and related these changes to glucose metabolism and the gut microbiome. C57Bl/6J mice fed low-...
Source: Free Radical Biology and Medicine - April 8, 2021 Category: Biology Authors: Charlene B Van Buiten Guojun Wu Yan Y Lam Liping Zhao Ilya Raskin Source Type: research

Elemental iron modifies the redox environment of the gastrointestinal tract: a novel therapeutic target and test for metabolic syndrome
Free Radic Biol Med. 2021 Apr 5:S0891-5849(21)00192-1. doi: 10.1016/j.freeradbiomed.2021.03.032. Online ahead of print.ABSTRACTMetabolic syndrome (MetS, i.e., type 2 diabetes and obesity) is often associated with dysbiosis, inflammation, and leaky gut syndrome, which increase the content of oxygen and reactive oxygen species (ROS) in the gastrointestinal (GI) tract. Using near-infrared fluorescent, in situ imaging of ROS, we evaluated the effects of oral administration of elemental iron powder (Fe0) on luminal ROS in the GI tract and related these changes to glucose metabolism and the gut microbiome. C57Bl/6J mice fed low-...
Source: Free Radical Biology and Medicine - April 8, 2021 Category: Biology Authors: Charlene B Van Buiten Guojun Wu Yan Y Lam Liping Zhao Ilya Raskin Source Type: research

Pretreatment with Kaempferol attenuates microglia-mediate neuroinflammation by inhibiting MAPKs-NF- κB signaling pathway and pyroptosis after secondary spinal cord injury
In conclusion, kaempferol was able to reduce oxidative stress and inflammatory response through down-regulation of ROS dependent MAPKs- NF-κB and pyroptosis signaling pathway, which suggested that kaempferol might be a novel promising therapeutic agent for SCI.PMID:33823244 | DOI:10.1016/j.freeradbiomed.2021.03.037 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 6, 2021 Category: Biology Authors: Zhongyuan Liu Xinqiang Yao Baihui Sun Wangsheng Jiang Congrui Liao Xiangheng Dai Yu Chen Jianting Chen Ruoting Ding Source Type: research

Detection of extracellular superoxide in isolated human immune cells and in an animal model of arterial hypertension using hydropropidine probe and HPLC analysis
In conclusion, the HPr+/HPLC assay for superoxide determination is highly reliable in isolated immune cells and an animal model of arterial hypertension. In particular, the cell impermeability of HPr+ made it possible to differentiate between intra- and extracellular superoxide formation.PMID:33823245 | DOI:10.1016/j.freeradbiomed.2021.03.041 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 6, 2021 Category: Biology Authors: Sanela Kalinovic Paul Stamm Matthias Oelze Sebastian Steven Swenja Kr öller-Schön Miroslava Kvandova Jacek Zielonka Thomas M ünzel Andreas Daiber Source Type: research

Pretreatment with Kaempferol attenuates microglia-mediate neuroinflammation by inhibiting MAPKs-NF- κB signaling pathway and pyroptosis after secondary spinal cord injury
In conclusion, kaempferol was able to reduce oxidative stress and inflammatory response through down-regulation of ROS dependent MAPKs- NF-κB and pyroptosis signaling pathway, which suggested that kaempferol might be a novel promising therapeutic agent for SCI.PMID:33823244 | DOI:10.1016/j.freeradbiomed.2021.03.037 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 6, 2021 Category: Biology Authors: Zhongyuan Liu Xinqiang Yao Baihui Sun Wangsheng Jiang Congrui Liao Xiangheng Dai Yu Chen Jianting Chen Ruoting Ding Source Type: research

Detection of extracellular superoxide in isolated human immune cells and in an animal model of arterial hypertension using hydropropidine probe and HPLC analysis
In conclusion, the HPr+/HPLC assay for superoxide determination is highly reliable in isolated immune cells and an animal model of arterial hypertension. In particular, the cell impermeability of HPr+ made it possible to differentiate between intra- and extracellular superoxide formation.PMID:33823245 | DOI:10.1016/j.freeradbiomed.2021.03.041 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 6, 2021 Category: Biology Authors: Sanela Kalinovic Paul Stamm Matthias Oelze Sebastian Steven Swenja Kr öller-Schön Miroslava Kvandova Jacek Zielonka Thomas M ünzel Andreas Daiber Source Type: research

Kinetic assessment of Michael addition reactions of alpha, beta-unsaturated carbonyl compounds to amino acid and protein thiols
Free Radic Biol Med. 2021 Apr 2:S0891-5849(21)00200-8. doi: 10.1016/j.freeradbiomed.2021.03.040. Online ahead of print.ABSTRACTHumans have extensive adverse exposure to alpha,beta-unsaturated carbonyl compounds (ABuCs) as these are major toxins in smoke and exhaust fumes, as well as products of lipid peroxidation. In contrast, another ABuC, dimethylfumarate, is used to treat psoriasis and multiple sclerosis. ABuCs undergo Michael adduction with amine, imidazole and thiol groups, with reaction at Cys residues predominating. Here we report rate constants, k2, for ABuCs (acrolein, crotonaldehyde, dimethylfumarate, cyclohex-1-...
Source: Free Radical Biology and Medicine - April 5, 2021 Category: Biology Authors: Max Sauerland Ralf Mertes Chiara Morozzi Aimee L Eggler Luke F Gamon Michael J Davies Source Type: research

Kinetic assessment of Michael addition reactions of alpha, beta-unsaturated carbonyl compounds to amino acid and protein thiols
Free Radic Biol Med. 2021 Apr 2:S0891-5849(21)00200-8. doi: 10.1016/j.freeradbiomed.2021.03.040. Online ahead of print.ABSTRACTHumans have extensive adverse exposure to alpha,beta-unsaturated carbonyl compounds (ABuCs) as these are major toxins in smoke and exhaust fumes, as well as products of lipid peroxidation. In contrast, another ABuC, dimethylfumarate, is used to treat psoriasis and multiple sclerosis. ABuCs undergo Michael adduction with amine, imidazole and thiol groups, with reaction at Cys residues predominating. Here we report rate constants, k2, for ABuCs (acrolein, crotonaldehyde, dimethylfumarate, cyclohex-1-...
Source: Free Radical Biology and Medicine - April 5, 2021 Category: Biology Authors: Max Sauerland Ralf Mertes Chiara Morozzi Aimee L Eggler Luke F Gamon Michael J Davies Source Type: research

Rosmarinic acid prevents refractory bacterial pneumonia through regulating Keap1/Nrf2-mediated autophagic pathway and mitochondrial oxidative stress
Free Radic Biol Med. 2021 Apr 1:S0891-5849(21)00198-2. doi: 10.1016/j.freeradbiomed.2021.03.038. Online ahead of print.ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of bacterial pneumonia, featured with exuberant inflammatory cytokine production, extensive oxidative stress and tissue injury. The Keap1/Nrf2 system is the major apparatus essential for host defense against oxidative and electrophilic stresses of both exogenous and endogenous origins, representing a logical target for host-directed strategy to treat severe inflammatory diseases including MRSA-induced pneumonia. In an effort to...
Source: Free Radical Biology and Medicine - April 4, 2021 Category: Biology Authors: Wei Zhang Cheng Cheng Zhou Sha Changmai Chen Chengtao Yu Nianyin Lv Peng Ji Xiaohui Wu Tonghui Ma Haibo Cheng Liyun Shi Source Type: research

Developing a novel strategy for COPD therapy by targeting Nrf2 and metabolism reprogramming simultaneously
Free Radic Biol Med. 2021 Apr 1:S0891-5849(21)00199-4. doi: 10.1016/j.freeradbiomed.2021.03.039. Online ahead of print.ABSTRACTChronic obstructive pulmonary disease (COPD) is estimated to be the sixth major cause of disability, and the third main cause of death in the world by 2020. Although both inflammation and oxidative stress are well known to be the key predisposing factors in the pathogenesis of COPD, other elements, including metabolism, may also contribute to the exacerbation of the disease. However, the therapeutic approach which alters metabolism against COPD has yet been fully developed. Therefore, here we provi...
Source: Free Radical Biology and Medicine - April 4, 2021 Category: Biology Authors: Li Wang Xinyi Chen Xiang Li Dongli Liu Xiaojun Wang Xiaohong Chang Youmin Guo Source Type: research

Rosmarinic acid prevents refractory bacterial pneumonia through regulating Keap1/Nrf2-mediated autophagic pathway and mitochondrial oxidative stress
Free Radic Biol Med. 2021 Apr 1:S0891-5849(21)00198-2. doi: 10.1016/j.freeradbiomed.2021.03.038. Online ahead of print.ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of bacterial pneumonia, featured with exuberant inflammatory cytokine production, extensive oxidative stress and tissue injury. The Keap1/Nrf2 system is the major apparatus essential for host defense against oxidative and electrophilic stresses of both exogenous and endogenous origins, representing a logical target for host-directed strategy to treat severe inflammatory diseases including MRSA-induced pneumonia. In an effort to...
Source: Free Radical Biology and Medicine - April 4, 2021 Category: Biology Authors: Wei Zhang Cheng Cheng Zhou Sha Changmai Chen Chengtao Yu Nianyin Lv Peng Ji Xiaohui Wu Tonghui Ma Haibo Cheng Liyun Shi Source Type: research

Developing a novel strategy for COPD therapy by targeting Nrf2 and metabolism reprogramming simultaneously
Free Radic Biol Med. 2021 Apr 1:S0891-5849(21)00199-4. doi: 10.1016/j.freeradbiomed.2021.03.039. Online ahead of print.ABSTRACTChronic obstructive pulmonary disease (COPD) is estimated to be the sixth major cause of disability, and the third main cause of death in the world by 2020. Although both inflammation and oxidative stress are well known to be the key predisposing factors in the pathogenesis of COPD, other elements, including metabolism, may also contribute to the exacerbation of the disease. However, the therapeutic approach which alters metabolism against COPD has yet been fully developed. Therefore, here we provi...
Source: Free Radical Biology and Medicine - April 4, 2021 Category: Biology Authors: Li Wang Xinyi Chen Xiang Li Dongli Liu Xiaojun Wang Xiaohong Chang Youmin Guo Source Type: research

Mitochondria-targeted prooxidant effects of betulinic acid conjugated with delocalized lipophilic cation F16
Free Radic Biol Med. 2021 Mar 31:S0891-5849(21)00196-9. doi: 10.1016/j.freeradbiomed.2021.03.036. Online ahead of print.ABSTRACTThe paper examines the molecular mechanisms of the cytotoxicity of conjugates of betulinic acid with the penetrating cation F16. The in vitro experiments on rat thymocytes revealed that all the obtained F16-betulinic acid derivatives showed more than 10-fold higher cytotoxicity as compared to betulinic acid and F16. In this case, 0.5-1 μM of all conjugates showed mitochondria-targeted action, inducing superoxide overproduction and reducing the mitochondrial potential of cells. Experiments on is...
Source: Free Radical Biology and Medicine - April 3, 2021 Category: Biology Authors: Mikhail V Dubinin Alena A Semenova Anna I Ilzorkina Nikita V Penkov Darya A Nedopekina Vyacheslav A Sharapov Ekaterina I Khoroshavina Eldar V Davletshin Natalia V Belosludtseva Anna Yu Spivak Konstantin N Belosludtsev Source Type: research

Higher systemic oxidatively generated DNA and RNA damage in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives
Free Radic Biol Med. 2021 Mar 30:S0891-5849(21)00182-9. doi: 10.1016/j.freeradbiomed.2021.03.022. Online ahead of print.ABSTRACTBACKGROUND: Prior studies in bipolar disorders (BD) have suggested that oxidative stress and cellular ageing play a key role in the pathophysiology of BD. Nevertheless, oxidative stress has not been investigated in patients with newly diagnosed BD and in their unaffected first-degree relatives (UR), compared with healthy control individuals (HC).METHODS: We investigated the level of systemic oxidative damage to DNA and RNA measured by urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo...
Source: Free Radical Biology and Medicine - April 2, 2021 Category: Biology Authors: Klara Coello Helena Lykke B øgh Sharleny Stanislaus Hanne Lie Kj ærstad Sigurd A Melbye Kimie Stefanie Ormstrup Sletved Henrik Enghusen Poulsen Maj Vinberg Lars Vedel Kessing Source Type: research

A Bioinspired Nitrone Precursor to a Stabilized Nitroxide Radical
Free Radic Biol Med. 2021 Mar 30:S0891-5849(21)00190-8. doi: 10.1016/j.freeradbiomed.2021.03.030. Online ahead of print.ABSTRACTNitrones derived from natural antioxidants are emerging as highly specific therapeutics against various human diseases, including stroke, neurodegenerative pathologies, and cancer. However, the development of useful pseudo-natural nitrones requires the judicious choice of a secondary metabolite as the precursor. Betalains are nitrogen-containing natural pigments that exhibit marked antioxidant capacity and pharmacological properties and, hence, are ideal candidates for designing multifunctional ni...
Source: Free Radical Biology and Medicine - April 2, 2021 Category: Biology Authors: Amanda Capistrano Pinheiro Rodrigo Boni Fazzi Larissa Cerrato Esteves Caroline Oliveira Machado Felipe Augusto D örr Ernani Pinto Yocefu Hattori Jacinto Sa Ana Maria da Costa Ferreira Erick Leite Bastos Source Type: research

A deleterious interplay between Endoplasmic reticulum stress and its functional linkage to Mitochondria in nephrolithiasis
In conclusion, our data showed that hyperoxaluria induces renal ER stress which triggers mitochondria dysfunction, might be via alteration in the sigma-1 receptor protein in the mitochondria-associated ER membranes, which leads to apoptosis, renal injury, and calcium oxalate crystal deposition.PMID:33798617 | DOI:10.1016/j.freeradbiomed.2021.03.031 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 2, 2021 Category: Biology Authors: Minu Sharma S Naura Amarjit S K Singla Source Type: research

Higher systemic oxidatively generated DNA and RNA damage in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives
Free Radic Biol Med. 2021 Mar 30:S0891-5849(21)00182-9. doi: 10.1016/j.freeradbiomed.2021.03.022. Online ahead of print.ABSTRACTBACKGROUND: Prior studies in bipolar disorders (BD) have suggested that oxidative stress and cellular ageing play a key role in the pathophysiology of BD. Nevertheless, oxidative stress has not been investigated in patients with newly diagnosed BD and in their unaffected first-degree relatives (UR), compared with healthy control individuals (HC).METHODS: We investigated the level of systemic oxidative damage to DNA and RNA measured by urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo...
Source: Free Radical Biology and Medicine - April 2, 2021 Category: Biology Authors: Klara Coello Helena Lykke B øgh Sharleny Stanislaus Hanne Lie Kj ærstad Sigurd A Melbye Kimie Stefanie Ormstrup Sletved Henrik Enghusen Poulsen Maj Vinberg Lars Vedel Kessing Source Type: research

A Bioinspired Nitrone Precursor to a Stabilized Nitroxide Radical
Free Radic Biol Med. 2021 Mar 30:S0891-5849(21)00190-8. doi: 10.1016/j.freeradbiomed.2021.03.030. Online ahead of print.ABSTRACTNitrones derived from natural antioxidants are emerging as highly specific therapeutics against various human diseases, including stroke, neurodegenerative pathologies, and cancer. However, the development of useful pseudo-natural nitrones requires the judicious choice of a secondary metabolite as the precursor. Betalains are nitrogen-containing natural pigments that exhibit marked antioxidant capacity and pharmacological properties and, hence, are ideal candidates for designing multifunctional ni...
Source: Free Radical Biology and Medicine - April 2, 2021 Category: Biology Authors: Amanda Capistrano Pinheiro Rodrigo Boni Fazzi Larissa Cerrato Esteves Caroline Oliveira Machado Felipe Augusto D örr Ernani Pinto Yocefu Hattori Jacinto Sa Ana Maria da Costa Ferreira Erick Leite Bastos Source Type: research

A deleterious interplay between Endoplasmic reticulum stress and its functional linkage to Mitochondria in nephrolithiasis
In conclusion, our data showed that hyperoxaluria induces renal ER stress which triggers mitochondria dysfunction, might be via alteration in the sigma-1 receptor protein in the mitochondria-associated ER membranes, which leads to apoptosis, renal injury, and calcium oxalate crystal deposition.PMID:33798617 | DOI:10.1016/j.freeradbiomed.2021.03.031 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 2, 2021 Category: Biology Authors: Minu Sharma S Naura Amarjit S K Singla Source Type: research

Compartmentally scavenging hepatic oxidants through AMPK/SIRT3-PGC1 α axis improves mitochondrial biogenesis and glucose catabolism
In this study, we found that compartmentally inhibiting hepatic oxidants by nano-MitoPBN, a liver mitochondrial-targeting ROS scavenger, could effectively prevent diabetes. Our results demonstrated that nano-MitoPBN reversed the downregulation of PGC-1α and the enhanced gluconeogenesis in the livers of diabetic mice. PGC-1α, through an AMPK- and SIRT3-mediated mechanism, promoted mitochondrial biogenesis, increased the number of mitochondria, and enhanced the rate of aerobic oxidation, leading to decreased glucose levels in the blood by increasing glucose uptake and catabolism in the liver. Moreover, the increa...
Source: Free Radical Biology and Medicine - April 1, 2021 Category: Biology Authors: Meiling Wu Chunwang Zhang Mengdan Xie Yuansheng Zhen Ben Lai Jiankang Liu Liang Qiao Shanlin Liu Dongyun Shi Source Type: research

Regulation of Nrf2 by phosphorylation: consequences for biological function and therapeutic implications
Free Radic Biol Med. 2021 Mar 29:S0891-5849(21)00194-5. doi: 10.1016/j.freeradbiomed.2021.03.034. Online ahead of print.ABSTRACTThe transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) participates in the activation of the antioxidant cytoprotective pathway and other important physiological processes to maintain cellular homeostasis. The dysregulation of NRF2 activity plays a role in various diseases, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Thus, NRF2 activity is tightly regulated through multiple mechanisms, among which phosphorylation by kinases is critical in the posttra...
Source: Free Radical Biology and Medicine - April 1, 2021 Category: Biology Authors: Tian Liu Yi-Fei Lv Jing-Long Zhao Qi-Dong You Zheng-Yu Jiang Source Type: research

Compartmentally scavenging hepatic oxidants through AMPK/SIRT3-PGC1 α axis improves mitochondrial biogenesis and glucose catabolism
In this study, we found that compartmentally inhibiting hepatic oxidants by nano-MitoPBN, a liver mitochondrial-targeting ROS scavenger, could effectively prevent diabetes. Our results demonstrated that nano-MitoPBN reversed the downregulation of PGC-1α and the enhanced gluconeogenesis in the livers of diabetic mice. PGC-1α, through an AMPK- and SIRT3-mediated mechanism, promoted mitochondrial biogenesis, increased the number of mitochondria, and enhanced the rate of aerobic oxidation, leading to decreased glucose levels in the blood by increasing glucose uptake and catabolism in the liver. Moreover, the increa...
Source: Free Radical Biology and Medicine - April 1, 2021 Category: Biology Authors: Meiling Wu Chunwang Zhang Mengdan Xie Yuansheng Zhen Ben Lai Jiankang Liu Liang Qiao Shanlin Liu Dongyun Shi Source Type: research

Regulation of Nrf2 by phosphorylation: consequences for biological function and therapeutic implications
Free Radic Biol Med. 2021 Mar 29:S0891-5849(21)00194-5. doi: 10.1016/j.freeradbiomed.2021.03.034. Online ahead of print.ABSTRACTThe transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) participates in the activation of the antioxidant cytoprotective pathway and other important physiological processes to maintain cellular homeostasis. The dysregulation of NRF2 activity plays a role in various diseases, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Thus, NRF2 activity is tightly regulated through multiple mechanisms, among which phosphorylation by kinases is critical in the posttra...
Source: Free Radical Biology and Medicine - April 1, 2021 Category: Biology Authors: Tian Liu Yi-Fei Lv Jing-Long Zhao Qi-Dong You Zheng-Yu Jiang Source Type: research

Targeting SLC3A2 subunit of system X < sub > C < /sub > < sup > - < /sup > is essential for m < sup > 6 < /sup > A reader YTHDC2 to be an endogenous ferroptosis inducer in lung adenocarcinoma
In conclusion, YTHDC2 is believed to be a powerful endogenous ferroptosis inducer and targeting SLC3A2 subunit of system XC- is essential for this process. Increasing YTHDC2 is an alternative ferroptosis-based therapy to treat LUAD.PMID:33785413 | DOI:10.1016/j.freeradbiomed.2021.03.023 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - March 31, 2021 Category: Biology Authors: Lifang Ma Xiao Zhang Keke Yu Xin Xu Tianxiang Chen Yi Shi Yikun Wang Shiyu Qiu Susu Guo Jiangtao Cui Yayou Miao Xiaoting Tian Lutao Du Yongchun Yu Jinjing Xia Jiayi Wang Source Type: research

The role of vitamin C in epigenetic cancer therapy
Free Radic Biol Med. 2021 Mar 28:S0891-5849(21)00169-6. doi: 10.1016/j.freeradbiomed.2021.03.017. Online ahead of print.NO ABSTRACTPMID:33789122 | DOI:10.1016/j.freeradbiomed.2021.03.017 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - March 31, 2021 Category: Biology Authors: Stine Ulrik Mikkelsen Linn Gillberg Jens Lykkesfeldt Kirsten Gr ønbæk Source Type: research

The roles of inducible chromatin and transcriptional memory in cellular defense system responses to redox-active pollutants
Free Radic Biol Med. 2021 Mar 28:S0891-5849(21)00177-5. doi: 10.1016/j.freeradbiomed.2021.03.018. Online ahead of print.ABSTRACTPeople are exposed to wide range of redox-active environmental pollutants. Air pollution, heavy metals, pesticides, and endocrine disrupting chemicals can disrupt cellular redox status. Redox-active pollutants in our environment all trigger their own sets of specific cellular responses, but they also activate a common set of general stress responses that buffer the cell against homeostatic insults. These cellular defense system (CDS) pathways include the heat shock response, the oxidative stress r...
Source: Free Radical Biology and Medicine - March 31, 2021 Category: Biology Authors: Caren Weinhouse Source Type: research

Nox4-Dependent Upregulation of S100A4 after Peripheral Nerve Injury Modulates Neuropathic Pain Processing
In this study, we aimed to identify novel Nox4 downstream interactors in the nociceptive system. Mice lacking Nox4 specifically in sensory neurons were generated by crossing Advillin-Cre mice with Nox4fl/fl mice. Tissue-specific deletion of Nox4 in sensory neurons considerably reduced mechanical hypersensitivity and neuronal action potential firing after peripheral nerve injury. Using a proteomic approach, we detected various proteins that are regulated in a Nox4-dependent manner after injury, including the small calcium-binding protein S100A4. Immunofluorescence staining and western blot experiments confirmed that S100A4 ...
Source: Free Radical Biology and Medicine - March 31, 2021 Category: Biology Authors: Gesine Wack Katharina Metzner Miriam S Kuth Elena Wang Anne Bresnick Ralf P Brandes Katrin Schr öder Ilka Wittig Achim Schmidtko Wiebke Kallenborn-Gerhardt Source Type: research

Novel perspectives on redox signaling in red blood cells and platelets in cardiovascular disease
Free Radic Biol Med. 2021 Mar 28:S0891-5849(21)00179-9. doi: 10.1016/j.freeradbiomed.2021.03.020. Online ahead of print.ABSTRACTThe fundamental physiology of circulating red blood cells (RBCs) and platelets involving regulation of oxygen transport and hemostasis, respectively, are well-described in the literature. Their abundance in the circulation and their interaction with the vascular wall and each other have attracted the attention of other putative physiological and pathophysiological effects of these cells. RBCs and platelets are both important regulators of redox balance harboring powerful pro-oxidant and anti-oxida...
Source: Free Radical Biology and Medicine - March 31, 2021 Category: Biology Authors: Ali Mahdi Miriam M Cortese-Krott Malte Kelm Nailin Li John Pernow Source Type: research

Targeting SLC3A2 subunit of system X < sub > C < /sub > < sup > - < /sup > is essential for m < sup > 6 < /sup > A reader YTHDC2 to be an endogenous ferroptosis inducer in lung adenocarcinoma
In conclusion, YTHDC2 is believed to be a powerful endogenous ferroptosis inducer and targeting SLC3A2 subunit of system XC- is essential for this process. Increasing YTHDC2 is an alternative ferroptosis-based therapy to treat LUAD.PMID:33785413 | DOI:10.1016/j.freeradbiomed.2021.03.023 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - March 31, 2021 Category: Biology Authors: Lifang Ma Xiao Zhang Keke Yu Xin Xu Tianxiang Chen Yi Shi Yikun Wang Shiyu Qiu Susu Guo Jiangtao Cui Yayou Miao Xiaoting Tian Lutao Du Yongchun Yu Jinjing Xia Jiayi Wang Source Type: research

The role of vitamin C in epigenetic cancer therapy
Free Radic Biol Med. 2021 Mar 28:S0891-5849(21)00169-6. doi: 10.1016/j.freeradbiomed.2021.03.017. Online ahead of print.NO ABSTRACTPMID:33789122 | DOI:10.1016/j.freeradbiomed.2021.03.017 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - March 31, 2021 Category: Biology Authors: Stine Ulrik Mikkelsen Linn Gillberg Jens Lykkesfeldt Kirsten Gr ønbæk Source Type: research

The roles of inducible chromatin and transcriptional memory in cellular defense system responses to redox-active pollutants
Free Radic Biol Med. 2021 Mar 28:S0891-5849(21)00177-5. doi: 10.1016/j.freeradbiomed.2021.03.018. Online ahead of print.ABSTRACTPeople are exposed to wide range of redox-active environmental pollutants. Air pollution, heavy metals, pesticides, and endocrine disrupting chemicals can disrupt cellular redox status. Redox-active pollutants in our environment all trigger their own sets of specific cellular responses, but they also activate a common set of general stress responses that buffer the cell against homeostatic insults. These cellular defense system (CDS) pathways include the heat shock response, the oxidative stress r...
Source: Free Radical Biology and Medicine - March 31, 2021 Category: Biology Authors: Caren Weinhouse Source Type: research

Nox4-Dependent Upregulation of S100A4 after Peripheral Nerve Injury Modulates Neuropathic Pain Processing
In this study, we aimed to identify novel Nox4 downstream interactors in the nociceptive system. Mice lacking Nox4 specifically in sensory neurons were generated by crossing Advillin-Cre mice with Nox4fl/fl mice. Tissue-specific deletion of Nox4 in sensory neurons considerably reduced mechanical hypersensitivity and neuronal action potential firing after peripheral nerve injury. Using a proteomic approach, we detected various proteins that are regulated in a Nox4-dependent manner after injury, including the small calcium-binding protein S100A4. Immunofluorescence staining and western blot experiments confirmed that S100A4 ...
Source: Free Radical Biology and Medicine - March 31, 2021 Category: Biology Authors: Gesine Wack Katharina Metzner Miriam S Kuth Elena Wang Anne Bresnick Ralf P Brandes Katrin Schr öder Ilka Wittig Achim Schmidtko Wiebke Kallenborn-Gerhardt Source Type: research

Novel perspectives on redox signaling in red blood cells and platelets in cardiovascular disease
Free Radic Biol Med. 2021 Mar 28:S0891-5849(21)00179-9. doi: 10.1016/j.freeradbiomed.2021.03.020. Online ahead of print.ABSTRACTThe fundamental physiology of circulating red blood cells (RBCs) and platelets involving regulation of oxygen transport and hemostasis, respectively, are well-described in the literature. Their abundance in the circulation and their interaction with the vascular wall and each other have attracted the attention of other putative physiological and pathophysiological effects of these cells. RBCs and platelets are both important regulators of redox balance harboring powerful pro-oxidant and anti-oxida...
Source: Free Radical Biology and Medicine - March 31, 2021 Category: Biology Authors: Ali Mahdi Miriam M Cortese-Krott Malte Kelm Nailin Li John Pernow Source Type: research

Epigenetic silencing of GTP cyclohydrolase 1 promotes hepatocellular carcinoma growth by activating superoxide anion-mediated ASK1/p38 signaling via inhibiting tetrahydrobiopterin de novo biosynthesis
Free Radic Biol Med. 2021 Mar 26:S0891-5849(21)00185-4. doi: 10.1016/j.freeradbiomed.2021.03.025. Online ahead of print.ABSTRACTMetabolic reprogramming is a hallmark of cancer, including hepatocellular carcinoma (HCC). However, its role in HCC remains to be elucidated. Herein, we identified GTP cyclohydrolase 1 (GCH1), the first rate-limiting enzyme in tetrahydrobiopterin (BH4) de novo biosynthesis, as a novel metabolic regulator of HCC. GCH1 was frequently down-regulated in HCC tissues and cell lines by promoter methylation. Low GCH1 expression was associated with larger tumor size, increased tumor number, and worse progn...
Source: Free Radical Biology and Medicine - March 30, 2021 Category: Biology Authors: Guo-Chao Zhong Zhi-Bo Zhao Yao Cheng Yun-Bing Wang Chan Qiu Lin-Hong Mao Jie-Jun Hu Dong Cai Yan Liu Jian-Ping Gong Sheng-Wei Li Source Type: research

DIP2A is involved in SOD-mediated antioxidative reactions in murine brain
Free Radic Biol Med. 2021 Mar 26:S0891-5849(21)00187-8. doi: 10.1016/j.freeradbiomed.2021.03.027. Online ahead of print.ABSTRACTAutism spectrum disorders (ASDs) are highly associated with oxidative stress. We have recently shown that Disconnected-interacting protein homolog 2 A (DIP2A) functions in ASD pathophysiology by regulating cortactin acetylation for spine development and synaptic transmission. However, its role is not fully understood in the context of its abundant expression in mitochondria. In this paper, we found that DIP2A was involved in superoxide dismutase (SOD)-mediated antioxidative reactions. In mice, DIP...
Source: Free Radical Biology and Medicine - March 30, 2021 Category: Biology Authors: Lu-Lu Bai Lu-Qing Zhang Jun Ma Jing Li Meng Tian Rang-Juan Cao Xiao-Xiao He Zi-Xuan He Hua-Li Yu Xiao-Juan Zhu Source Type: research

Importance of stem cell culture conditions for their derived extracellular vesicles therapeutic effect
Free Radic Biol Med. 2021 Mar 26:S0891-5849(21)00188-X. doi: 10.1016/j.freeradbiomed.2021.03.028. Online ahead of print.ABSTRACTStem cell-derived extracellular vesicles (EVs) could be enhanced by modifying specific in vitro parameters when culturing their originating stem cells. Controlling stem cell growth conditions with physical properties, oxygen tension and media preconditioning with soluble factors may influence EVs biogenesis and EVs biological function as well. Unfortunately, many misconceptions and methodological issues have hampered the progress in understanding the biological properties of EVs. In this review we...
Source: Free Radical Biology and Medicine - March 30, 2021 Category: Biology Authors: Cristina Mas-Bargues Consuelo Borr ás Source Type: research

Ginkgolide B monotherapy reverses osteoporosis by regulating oxidative stress-mediated bone homeostasis
Free Radic Biol Med. 2021 Mar 26:S0891-5849(21)00160-X. doi: 10.1016/j.freeradbiomed.2021.03.008. Online ahead of print.ABSTRACTOsteoporosis is characterized by reductions in bone mass, which could be attributed to the dysregulation of bone homeostasis, such as the loss of balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Elevated levels of oxidative stress increase bone resorption by promoting osteoclastogenesis and inhibiting the osteogenesis. Ginkgolide B (GB), a small natural molecule from Ginkgo biloba, has been reported to possess pharmacological activities by regulating reactive oxygen species...
Source: Free Radical Biology and Medicine - March 30, 2021 Category: Biology Authors: Chien-Wei Lee Hui-Chu Lin Belle Yu-Hsuan Wang Amanda Yu-Fan Wang Rita Lih-Ying Shin Stella Yee Lo Cheung Oscar Kuang-Sheng Lee Source Type: research

Epigenetic silencing of GTP cyclohydrolase 1 promotes hepatocellular carcinoma growth by activating superoxide anion-mediated ASK1/p38 signaling via inhibiting tetrahydrobiopterin de novo biosynthesis
Free Radic Biol Med. 2021 Mar 26:S0891-5849(21)00185-4. doi: 10.1016/j.freeradbiomed.2021.03.025. Online ahead of print.ABSTRACTMetabolic reprogramming is a hallmark of cancer, including hepatocellular carcinoma (HCC). However, its role in HCC remains to be elucidated. Herein, we identified GTP cyclohydrolase 1 (GCH1), the first rate-limiting enzyme in tetrahydrobiopterin (BH4) de novo biosynthesis, as a novel metabolic regulator of HCC. GCH1 was frequently down-regulated in HCC tissues and cell lines by promoter methylation. Low GCH1 expression was associated with larger tumor size, increased tumor number, and worse progn...
Source: Free Radical Biology and Medicine - March 30, 2021 Category: Biology Authors: Guo-Chao Zhong Zhi-Bo Zhao Yao Cheng Yun-Bing Wang Chan Qiu Lin-Hong Mao Jie-Jun Hu Dong Cai Yan Liu Jian-Ping Gong Sheng-Wei Li Source Type: research

DIP2A is involved in SOD-mediated antioxidative reactions in murine brain
Free Radic Biol Med. 2021 Mar 26:S0891-5849(21)00187-8. doi: 10.1016/j.freeradbiomed.2021.03.027. Online ahead of print.ABSTRACTAutism spectrum disorders (ASDs) are highly associated with oxidative stress. We have recently shown that Disconnected-interacting protein homolog 2 A (DIP2A) functions in ASD pathophysiology by regulating cortactin acetylation for spine development and synaptic transmission. However, its role is not fully understood in the context of its abundant expression in mitochondria. In this paper, we found that DIP2A was involved in superoxide dismutase (SOD)-mediated antioxidative reactions. In mice, DIP...
Source: Free Radical Biology and Medicine - March 30, 2021 Category: Biology Authors: Lu-Lu Bai Lu-Qing Zhang Jun Ma Jing Li Meng Tian Rang-Juan Cao Xiao-Xiao He Zi-Xuan He Hua-Li Yu Xiao-Juan Zhu Source Type: research

Importance of stem cell culture conditions for their derived extracellular vesicles therapeutic effect
Free Radic Biol Med. 2021 Mar 26:S0891-5849(21)00188-X. doi: 10.1016/j.freeradbiomed.2021.03.028. Online ahead of print.ABSTRACTStem cell-derived extracellular vesicles (EVs) could be enhanced by modifying specific in vitro parameters when culturing their originating stem cells. Controlling stem cell growth conditions with physical properties, oxygen tension and media preconditioning with soluble factors may influence EVs biogenesis and EVs biological function as well. Unfortunately, many misconceptions and methodological issues have hampered the progress in understanding the biological properties of EVs. In this review we...
Source: Free Radical Biology and Medicine - March 30, 2021 Category: Biology Authors: Cristina Mas-Bargues Consuelo Borr ás Source Type: research