Direct detection of 8-oxo-dG using nanopore sequencing DOI Creative Commons
Marc Pagès-Gallego, Daan M. K. van Soest, Nicolle Besselink

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 20, 2024

Abstract Genomic DNA is constantly subjected to oxidative damage, which thought be one of the major drivers cancer and age-dependent decline. The most prominent consequence modification guanine into 8-hydroxyguanine (8-oxo-dG), has important mutagenic potential plays a role in methylation-mediated gene regulation. Methods simultaneously detect quantify 8-oxo-dG within its genomic context have been lacking; mainly because these methods rely on indirect detection or are based hydrolysis DNA. Nanopore sequencing deployed for direct base-modifications like cytosine methylation during sequencing. However, currently there no model by nanopore due lack training data. Here, we developed strategy synthetic oligos create long molecules with variability effective deep learning Moreover, showcase approach suitable deal extreme scarceness compared canonical G enable specific detection. Applied an inducible tissue culture system our reveals variable distribution across genome, dissimilar pattern C>A mutations, concurrent 5-mC depletion 2-kilobase window surrounding sites. These findings not only underscore epigenetic research, but also shed light 8-oxo-dG’s By measuring at single molecule resolution, study provides insights functional interplay between modifications. using generate ground truth from machine calling could applied any other modification. Overall, work contributes advancing field epigenetics highlights as powerful tool studying

Language: Английский

ROS production by mitochondria: function or dysfunction? DOI
Flávio R. Palma, Benjamin N. Gantner,

Marcelo J. Sakiyama

et al.

Oncogene, Journal Year: 2023, Volume and Issue: 43(5), P. 295 - 303

Published: Dec. 11, 2023

Language: Английский

Citations

167
Targeting ROS in cancer: rationale and strategies DOI
Christophe Glorieux, Shihua Liu, Dunyaporn Trachootham

et al.

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(8), P. 583 - 606

Published: July 9, 2024

Language: Английский

Citations

137
Fundamentals of redox regulation in biology DOI
Helmut Sies, Ryan J. Mailloux,

Ursula Jakob

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(9), P. 701 - 719

Published: April 30, 2024

Language: Английский

Citations

125
Stress, epigenetics, and aging: Unraveling the intricate crosstalk DOI Creative Commons
Zeming Wu, Jing Qu, Weiqi Zhang

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 84(1), P. 34 - 54

Published: Nov. 13, 2023

Language: Английский

Citations

54
Biochemical and cellular basis of oxidative stress: Implications for disease onset DOI Creative Commons

Karl Aramouni,

Roland Assaf,

Abdullah Shaito

et al.

Journal of Cellular Physiology, Journal Year: 2023, Volume and Issue: 238(9), P. 1951 - 1963

Published: July 12, 2023

Abstract Cellular oxidation–reduction (redox) systems, which encompass pro‐ and antioxidant molecules, are integral components of a plethora essential cellular processes. Any dysregulation these systems can cause molecular imbalances between the moieties, leading to state oxidative stress. Long‐lasting stress manifest clinically as variety chronic illnesses including cancers, neurodegenerative disorders, cardiovascular disease, metabolic diseases like diabetes. As such, this review investigates impact on human body with emphasis underlying oxidants, mechanisms, pathways. It also discusses available defense mechanisms. The monitoring regulatory that ensure balanced environment detailed. We critically discuss notion oxidants double‐edged sword, being signaling messengers at low physiological concentrations but causative agents when overproduced. In regard, presents strategies employed by redox activation transcriptional programs such those mediated Nrf2/Keap1 NFk signaling. Likewise, switches peroxiredoxin DJ‐1 proteins they regulate presented. concludes thorough comprehension is develop evolving field medicine.

Language: Английский

Citations

49
Oxidative Stress and Age-Related Tumors DOI Creative Commons
Emma Di Carlo, Carlo Sorrentino

Antioxidants, Journal Year: 2024, Volume and Issue: 13(9), P. 1109 - 1109

Published: Sept. 13, 2024

Oxidative stress is the result of imbalance between reactive oxygen and nitrogen species (RONS), which are produced by several endogenous exogenous processes, antioxidant defenses consisting molecules that protect biological systems from free radical toxicity. a major factor in aging process, contributing to accumulation cellular damage over time. biomolecules, leads DNA alterations, lipid peroxidation, protein oxidation, mitochondrial dysfunction resulting senescence, immune system tissue dysfunctions, increased susceptibility age-related pathologies, such as inflammatory disorders, cardiovascular neurodegenerative diseases, diabetes, cancer. stress-driven mutations, or methylation histone modification, alter gene expression, key determinants tumor initiation, angiogenesis, metastasis, therapy resistance. Accumulation genetic epigenetic damage, oxidative contributes, eventually unrestrained cell proliferation, inhibition differentiation, evasion death, providing favorable conditions for tumorigenesis. Colorectal, breast, lung, prostate, skin cancers most frequent aging-associated malignancies, implicated their pathogenesis behavior. Our aim shed light on molecular mechanisms link stress, aging, cancers, highlighting impact both RONS antioxidants, provided diet exercise, immunity, development an antitumor response. The dual role ROS physiological regulators signaling responsible well its use anti-tumor therapeutic purposes, will also be discussed. Managing crucial promoting healthy reducing risk tumors.

Language: Английский

Citations

21
Photo-responsive polydopamine nanoenzyme microneedles with oxidative stress regulation ability for atopic dermatitis treatment DOI
Yuanyuan Zhang, Xiao‐Xuan Zhang,

Xiangyi Wu

et al.

Nano Today, Journal Year: 2024, Volume and Issue: 56, P. 102241 - 102241

Published: March 28, 2024

Language: Английский

Citations

19
Flavonoids and their role in oxidative stress, inflammation, and human diseases DOI Creative Commons
Klaudia Jomová, Suliman Yousef Alomar,

Richard Valko

et al.

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: unknown, P. 111489 - 111489

Published: March 1, 2025

Oxidative stress and chronic inflammation are important drivers in the pathogenesis progression of many diseases, such as cancers breast, kidney, lung, others, autoimmune diseases (rheumatoid arthritis), cardiovascular (hypertension, atherosclerosis, arrhythmia), neurodegenerative (Alzheimer's disease, Parkinson's Huntington's disease), mental disorders (depression, schizophrenia, bipolar disorder), gastrointestinal (inflammatory bowel colorectal cancer), other disorders. With increasing demand for less toxic more tolerable therapies, flavonoids have potential to effectively modulate responsiveness conventional therapy radiotherapy. Flavonoids polyphenolic compounds found fruits, vegetables, grains, plant-derived beverages. Six twelve structurally different flavonoid subgroups dietary significance include anthocyanidins (e.g. pelargonidin, cyanidin), flavan-3-ols epicatechin, epigallocatechin), flavonols quercetin, kaempferol), flavones luteolin, baicalein), flavanones hesperetin, naringenin), isoflavones (daidzein, genistein). The health benefits related their structural characteristics, number position hydroxyl groups presence C2=C3 double bonds, which predetermine ability chelate metal ions, terminate ROS radicals formed by Fenton reaction), interact with biological targets trigger a response. Based on these can exert both antioxidant or prooxidant properties, activity ROS-scavenging enzymes expression activation proinflammatory cytokines (e.g., interleukin-1beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)), induce apoptosis autophagy, target key signaling pathways, nuclear factor erythroid 2-related 2 (Nrf2) Bcl-2 family proteins. This review aims briefly discuss mutually interconnected aspects oxidative inflammatory mechanisms, lipid peroxidation, protein oxidation, DNA damage, mechanism resolution inflammation. major part this article discusses role alleviating inflammation, two common components human diseases. results epidemiological studies also presented.

Language: Английский

Citations

5
Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis DOI Creative Commons
Jing Wang,

Chunshuang Li,

Jinling Han

et al.

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: Jan. 1, 2025

Abstract ROS cause multiple forms of DNA damage, and among them, 8-oxoguanine (8-oxoGua), an oxidized product guanine, is one the most abundant. If left unrepaired, 8-oxoGua may pair with A instead C, leading to a mutation G: C T: during replication. 8-Oxoguanine glycosylase 1 (OGG1) tailored repair enzyme that recognizes in duplex initiates base excision (BER) pathway remove lesion ensure fidelity genome. The accumulation genomic dysfunction OGG1 readily linked mutagenesis, subsequently aging-related diseases tumorigenesis; however, direct experimental evidence has long been lacking. Recently, series studies have shown guanine oxidation genome conservative bias, tendency occur regulatory regions, thus, not only be repaired, but also epigenetic modification. In this regard, specific reader Substrate recognition and/or by can conformation changes, affect chromatin modifications, thereby modulating transcription genes involved variety cellular processes, including inflammation, cell proliferation, differentiation, apoptosis. Thus, addition potential mutagenicity, contribute tumor development progression through altered gene expression stemming from its effects.

Language: Английский

Citations

2
From polyphenol to o‐quinone: Occurrence, significance, and intervention strategies in foods and health implications DOI
Yaqian Geng, Xinyu Liu,

Yiran Yu

et al.

Comprehensive Reviews in Food Science and Food Safety, Journal Year: 2023, Volume and Issue: 22(4), P. 3254 - 3291

Published: May 23, 2023

Polyphenol oxidation is a chemical process impairing food freshness and other desirable qualities, which has become serious problem in fruit vegetable processing industry. It crucial to understand the mechanisms involved these detrimental alterations. o-Quinones are primarily generated by polyphenols with di/tri-phenolic groups through enzymatic and/or auto-oxidation. They highly reactive species, not only readily suffer attack nucleophiles but also powerfully oxidize molecules presenting lower redox potentials via electron transfer reactions. These reactions subsequent complicated capable of initiating quality losses foods, such as browning, aroma loss, nutritional decline. To attenuate adverse influences, variety technologies have emerged restrain polyphenol governing different factors, especially oxidases oxygen. Despite tremendous efforts devoted, date, loss caused quinones remained great challenge Furthermore, o-quinones responsible for chemopreventive effects toxicity parent catechols on human health, quite complex. Herein, this review focuses generation reactivity o-quinones, attempting clarify deterioration foods health implications humans. Potential innovative inhibitors presented intervene o-quinone formation In future, feasibility inhibitory strategies should be evaluated, further exploration biological targets necessity.

Language: Английский

Citations

36