Advances in Redox Research

Amyloid aggregates are responsible for the development of oxidative stress and neurotoxicity in the brain. Several amino acid residues of amyloid beta (Aβ) 42 establish different molecular interactions to form and stabilize these aggregates, which can be targeted to prevent the aggregation. Resveratrol (Res) has inhibitory properties against Aβ 42 aggregation but studies elucidating its interactions with different residues of Aβ 42 aggregates are scarce. In the present study, we have discerned the molecular interactions of Res with different amino acid residues of Aβ 42 peptide and fibril during in-vitro Aβ 42 aggregation. Inhibitory properties of Res against amyloid aggregation were established through ANS and Thioflavin-T fluorescence assay, congo red assay and CD spectroscopy. The molecular interactions were established through molecular docking and 100 ns molecular dynamics simulations. The hydrophobic regions of Aβ 42 peptide, responsible for the formation of aggregates, were better protected in the presence of Res as indicated by ANS assay. Th-T and congo red assay suggested that Res prevented the formation of cross β-sheet structures. CD spectra analysis revealed that in the presence of Res, the secondary structure content was significantly decreased. MD simulation analysis revealed that Res formed strong molecular interactions with hydrophobic and secondary structure forming amino acid residues, which are involved in the amyloid aggregation and stabilization of aggregates. In conclusion, these interactions might have led to the decline in secondary structure content, formation of unordered nontoxic aggregates and prevention of the formation of sufuranyl free radical.

Sheetal Sharma

Hemant Goyal

Shubhi Joshi

Bimla Nehru

Avneet Saini

Molecular interactions of resveratrol with Aβ 42 peptide and fibril during in-vitro Aβ 42 aggregation

白藜芦醇与Aβ 42肽及其纤维在体外Aβ 42聚集过程中的分子相互作用

Oxidative stress (OS) is a phenomenon caused by an imbalance between free-radical production and antioxidant activity within the body. Status of endogenous antioxidants is not always sufficient to mitigate the oxidative damage. In this case, exogenous antioxidants could help to minimize free-radical production and subsequent OS. Green tea is rich in several phenolic compounds that have strong antioxidant properties. However, their mechanism of action is still unclear. Hence, the present study aims to investigate binding affinities of six green tea polyphenols such as catechin, epicatechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, and gallocatechin for common ROS producers such as Lipoxygenase (LOX), CYP2C9, and NAD(P)H oxidase (NOX). Results indicated that polyphenols interacted with binding pockets of these enzymes through hydrogen bonds and other stable interactions such as van der waals, Pi-Pi, Pi-alkyl, and alkyl. All polyphenols showed varied binding affinities. Among them, epigallocatechin gallate and epigallocatechin showed the highest binding affinities for the ROS producers. Findings of the present study suggest that, apart from free radical scavenging activity, green tea polyphenols may directly interact with binding pockets of LOX, CYP2C9, and NOX to dampen ROS production and OS. However, studies involving animal models are required for additional validation of results.

Prem Rajak

Abhratanu Ganguly

Moutushi Mandi

Anik Dutta

Saurabh Sarkar

Sayantani Nanda

Kanchana Das

Siddhartha Ghanty

Gopal Biswas

In silico targeting of lipoxygenase, CYP2C9, and NAD(P)H oxidase by major green tea polyphenols to subvert oxidative stress

主要绿茶多酚通过计算机模拟靶向脂氧合酶、CYP2C9和NAD(P)H氧化酶以逆转氧化应激

Since the first years of this century, evidence of the generation of singlet oxygen and endogenous ozone from antibodies and some amino acids has been reported. Different mechanisms of action have been proposed which provide appropriate pathways that scientifically justify their approval. On the other hand, parenteral systemic ozone therapy is known to produce reactive oxygen species (ROS) that by chemical interconversion could form singlet oxygen, which is the precursor to trigger the formation of endogenous ozone. This article analyzes the latest evidences reported on the generation of biological ozone, and highlights the hypothesis that ROS resulting from the application of parenteral ozone therapy can also lead to the endogenous formation of ozone or an oxidant like ozone. Future confirmation of this approach would be another justification for the usefulness of ozone therapy in the treatment of diseases such as viral ones and antibiotic resistance.

Maritza F. Díaz-Gómez

Frank Hernández-Rosales

Can systemic parenteral ozone therapy generate biological ozone? A new hypothesis

系统性肠外臭氧疗法能否产生生物臭氧？一种新假说

The liver is provided with peculiar regenerative features, initiated by resection or acute/chronic injuries. Preservation of cell phenotype ("phenotypic fidelity") characterizes liver regeneration triggered by resection and acute damage. On the contrary, this mechanism is defective during chronic liver injury, in which regeneration can be supported by activation of facultative progenitors or trans-differentiation of parenchymal cells. Both resection and acute/chronic damages may alter hepatic redox homeostasis. This modification may impact the regulation of pathways involved in liver regeneration, including proliferation and trans-differentiation of parenchymal cells, as well as activation of facultative progenitors. The regenerative process of the liver may be modulated by several redox-dependent transcription factors. Among them, the nuclear factor erythroid 2-related factor 2 (NRF2) plays a determinant role. After hepatic resection, NRF2 contributes to the regulation of parenchymal proliferation, maintaining newly regenerated hepatocytes completely differentiated. NRF2 deactivation induces oxidative stress-related insulin resistance and impairs regeneration by blocking pro-mitogenic and anti-apoptotic pathways. This review summarizes evidence on the commitment of NRF2 in several mechanisms involved in liver regeneration. Pharmacological stimulation of NRF2 boosts liver mass recovery after partial hepatectomy. Furthermore, when p21 overexpression inhibits hepatocellular proliferation, NRF2 modulates trans-differentiation of cholangiocytes toward hepatocytes. Of interest, activation and differentiation of hepatic progenitors is associated with NRF2 inhibition. Current reports suggest that NRF2 modulation could pave the way for viable therapies to be tested in clinical trials.

Francesco Bellanti

Gaetano Serviddio

Gianluigi Vendemiale

Modulation of liver regeneration by the nuclear factor erythroid 2-related factor 2

核因子红系2相关因子2对肝脏再生的调控

Cadmium (Cd) is a toxic environmental metal that interacts with selenium (Se) and contributes to many lung diseases. Humans have widespread exposures to Cd through diet and cigarette smoking, and studies in rodent models show that Se can protect against Cd toxicities. We sought to identify whether an antagonistic relationship existed between Se and Cd burdens and determine whether this relationship may associate with metabolic variation within human lungs. We performed metabolomics of 31 human lungs, including 25 with end-stage lung disease due to idiopathic pulmonary fibrosis, cystic fibrosis, chronic obstructive lung disease (COPD)/emphysema and other causes, and 6 non-diseased lungs. Results showed pathway associations with Cd including amino acid, lipid and energy-related pathways. Metabolic pathways varying with Se had considerable overlap with these pathways. Hierarchical cluster analysis (HCA) of individuals according to metabolites associated with Cd showed partial separation of disease types, with COPD/emphysema in the cluster with highest Cd, and non-diseased lungs in the cluster with the lowest Cd. When compared to HCA of metabolites associated with Se, the results showed that the cluster containing COPD/emphysema had the lowest Se, and the non-diseased lungs had the highest Se. A greater number of pathway associations occurred for Cd to Se ratio than either Cd or Se alone, indicating that metabolic patterns were more dependent on Cd to Se ratio than on either alone. Network analysis of interactions of Cd and Se showed network centrality was associated with pathways linked to polyunsaturated fatty acids involved in inflammatory signaling. Overall, the data show that metabolic pathway responses in human lung vary with Cd and Se in a pattern suggesting that Se is antagonistic to Cd toxicity in humans.

Matthew Ryan Smith

Xin Hu

Zachery R Jarrell

Xiaojia He

Michael Orr

Jolyn Fernandes

Joshua D. Chandler

Douglas I. Walker

Annette Esper

Lucian Marts

David C. Neujahr

Dean P. Jones

Young-Mi Go

Study on the relationship between selenium and cadmium in diseased human lungs

人肺疾病中硒与镉关系的研究

Sarah E. Lacher

Tessa Schumann

Ryan Peters

Christopher Migliaccio

Andrij Holian

Matthew Slattery

NRF2 Protects Lung Epithelial Cells from Wood Smoke Particle Toxicity

NRF2保护肺上皮细胞免受木材烟雾颗粒毒性

Jibon Kumar Paul

Mahir Azmal

ANM Shah Newaz Been Haque

Omar Faruk Talukder

Meghla Meem

Ajit Ghosh

Phytochemical-Mediated Modulation of Signaling Pathways: A Promising Avenue for Drug Discovery

植物化学介导的信号通路调控：药物发现的新途径

Tomoya Suzuki

Ryoya Tetsuka

Atsuya Iwasaki

Tsutomu Shimura

Ryoichi Hirayama

Asako J Nakamura

Piceatannol reduces radiation-induced DNA double-strand breaks by suppressing superoxide production and enhancing ATM-dependent repair efficiency

白藜芦醇通过抑制超氧化物生成和增强ATM依赖性修复效率减少辐射诱导的DNA双链断裂

Soumyajit Mukherjee

Shubhojit Das

Sourav Kumar Patra

Mayukh Das

Sanjay Ghosh

Alok Ghosh

Absence of mitochondrial CX9C-CX10C protein Cox12 generates oxidative and nitrosative stress in Saccharomyces cerevisiae: Implication on cellular redox homeostasis

线粒体CX9C-CX10C蛋白Cox12缺失在酿酒酵母中产生氧化和亚硝化应激：对细胞氧化还原稳态的影响

Cervical cancer, a major global health issue and the fourth most common cancer among women, is strongly linked to Human Papillomavirus (HPV) infection. Emerging evidence indicates that oxidative stress plays a critical role in the carcinogenesis of cervical tissue. This study investigates the relationship between oxidative stress markers—specifically oxysterols, lipid oxidation, and protein carbonylation—and the progression of cervical neoplasia. Oxysterols, which are elevated in various inflammatory diseases and cancers, were measured in cervicovaginal fluid samples using LC-MS/MS. The targeted oxysterols included 27-hydroxycholesterol (27-OHC), 7β-hydroxycholesterol (7β-OHC), 7-ketocholesterol (7-KC), and 7α,27-dihydroxycholesterol (7α,27-diOHC). Among these, 7α,27-dihydroxycholesterol was significantly increased in correlation with the severity of neoplastic stages. In parallel, protein carbonylation, an indicator of cellular oxidative stress, was assessed. Results revealed higher levels of protein carbonylation in neoplastic samples compared to non-neoplastic controls. These modifications were further analysed through redox proteomics to identify the specific proteins affected. The study demonstrates that elevated lipid oxidation and protein carbonylation in cervicovaginal secretions are linked to the development and progression of cervical cancer. Identifying these biomarkers may improve screening strategies, enabling the identification of individuals at increased risk for cervical neoplasia and guiding timely interventions.

Busra Kose

Serkan Erkanlı

Alper Koçak

Coskun Guzel

Theo Luider

Irundika H.K. Dias

A. Tarik Baykal

Exploring Oxysterols and Protein Carbonylation in Cervicovaginal Secretions as Biomarkers for Cervical Cancer Development

探索宫颈阴道分泌物中的氧化固醇和蛋白质羰基化作为宫颈癌发展的生物标志物

u9zg3I	redox signalingreactive oxygen speciesoxidative stressantioxidantsredox triggered disease states
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ak9yM6	A7IHrH: 2021，sQJ/D8: ，sE9og+:， wzlKC/:
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Advances in Redox Research

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Molecular interactions of resveratrol with Aβ 42 peptide and fibril during in-vitro Aβ 42 aggregation

In silico targeting of lipoxygenase, CYP2C9, and NAD(P)H oxidase by major green tea polyphenols to subvert oxidative stress

Can systemic parenteral ozone therapy generate biological ozone? A new hypothesis

Modulation of liver regeneration by the nuclear factor erythroid 2-related factor 2

Study on the relationship between selenium and cadmium in diseased human lungs

NRF2 Protects Lung Epithelial Cells from Wood Smoke Particle Toxicity

Phytochemical-Mediated Modulation of Signaling Pathways: A Promising Avenue for Drug Discovery

Piceatannol reduces radiation-induced DNA double-strand breaks by suppressing superoxide production and enhancing ATM-dependent repair efficiency

Absence of mitochondrial CX9C-CX10C protein Cox12 generates oxidative and nitrosative stress in Saccharomyces cerevisiae: Implication on cellular redox homeostasis

Exploring Oxysterols and Protein Carbonylation in Cervicovaginal Secretions as Biomarkers for Cervical Cancer Development