New Approach Methods (NAMs) for Genotoxicity Assessment of Nano- and Advanced Materials; Advantages and Challenges DOI

Arno C. Gutleb,

Sivakumar Murugadoss,

Maciej Stępnik

и другие.

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Год журнала: 2025, Номер unknown, С. 503867 - 503867

Опубликована: Март 1, 2025

Язык: Английский

Environmental and Health Impacts of Graphene and Other Two-Dimensional Materials: A Graphene Flagship Perspective DOI Creative Commons

Hazel Lin,

Tina Buerki‐Thurnherr, Jasreen Kaur

и другие.

ACS Nano, Год журнала: 2024, Номер 18(8), С. 6038 - 6094

Опубликована: Фев. 13, 2024

Two-dimensional (2D) materials have attracted tremendous interest ever since the isolation of atomically thin sheets graphene in 2004 due to specific and versatile properties these materials. However, increasing production use 2D necessitate a thorough evaluation potential impact on human health environment. Furthermore, harmonized test protocols are needed with which assess safety The Graphene Flagship project (2013-2023), funded by European Commission, addressed identification possible hazard graphene-based as well emerging including transition metal dichalcogenides, hexagonal boron nitride, others. Additionally, so-called green chemistry approaches were explored achieve goal safe sustainable this fascinating family nanomaterials. present review provides compact survey findings lessons learned Flagship.

Язык: Английский

Процитировано

25

Toxicity effects of pesticides based on zebrafish (Danio rerio) models: Advances and perspectives DOI
Jiajia Cui,

Sinuo Tian,

Yuntong Gu

и другие.

Chemosphere, Год журнала: 2023, Номер 340, С. 139825 - 139825

Опубликована: Авг. 14, 2023

Язык: Английский

Процитировано

32

Diclofenac eco-geno-toxicity in freshwater algae, rotifers and crustaceans DOI Creative Commons
Chiara Russo, Roberta Nugnes, Elena Orlo

и другие.

Environmental Pollution, Год журнала: 2023, Номер 335, С. 122251 - 122251

Опубликована: Июль 26, 2023

This study assessed the eco-genotoxic impact of diclofenac (DCF) in sentinel species freshwater ecosystem. DCF residues are found from few ng/L to tens μg/L due inability conventional wastewater treatment plants ensure removal efficiency drug. An ample body literature reports on acute toxicity non-target organisms without addressing potential chronic long-term effects at actual, environmental concentrations. Herein, assessment for and was performed vivo exposed DCF, specifically green alga Raphidocelis subcapitata, rotifer Brachionus calyciflorus crustacean Ceriodaphnia dubia. Furthermore, DNA damage expression antioxidant genes (MnSOD, Cu/ZnSOD CAT) were evaluated neonates. The toxicological risk as well its. GENOTOXIC RISK: observed concentrations far those concern. Rotifers crustaceans much more chronically sensitive than algae observing besides, median effect μg/L. In crustaceans, noted units μg/L, revealing dysregulated activity SOD CAT also showed ability provoke oxidative stress. On risk, Risk Quotient (RQ) above threshold value 1. Nevertheless, genotoxic RQ significantly greater RQ, thus, need regulatory bodies acknowledge an factor. To our knowledge, this is first investigation perform DCF.

Язык: Английский

Процитировано

25

Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review DOI Open Access
Nilesh Kumar Sharma, Anjali Bahot,

Gopinath Sekar

и другие.

Cancers, Год журнала: 2024, Номер 16(4), С. 680 - 680

Опубликована: Фев. 6, 2024

In recent years, the emergence of cancer drug resistance has been one crucial tumor hallmarks that are supported by level genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression ABC transporters, stemness among several key contributing molecular response mechanisms. Topo-active drugs, e.g., doxorubicin topotecan, clinically active utilized extensively against a wide variety human tumors often result in development failure to therapy. Thus, there is an urgent need for incremental comprehensive understanding mechanisms specifically context topo-active drugs. This review delves into intricate mechanistic aspects these intracellular extracellular explores use potential combinatorial approaches utilizing various drugs inhibitors pathways involved resistance. We believe this will help guide basic scientists, pre-clinicians, clinicians, policymakers toward holistic interdisciplinary strategies transcend resistance, renewing optimism ongoing battle cancer.

Язык: Английский

Процитировано

15

A scalable synthesis of adjuvanting antigen depots based on metal–organic frameworks DOI Creative Commons
Ryanne N. Ehrman, Olivia R. Brohlin, Yalini H. Wijesundara

и другие.

Chemical Science, Год журнала: 2024, Номер 15(8), С. 2731 - 2744

Опубликована: Янв. 1, 2024

Vaccines have saved countless lives by preventing and even irradicating infectious diseases. Commonly used subunit vaccines comprising one or multiple recombinant proteins isolated from a pathogen demonstrate better safety profile than live attenuated vaccines. However, the immunogenicity of these is weak, therefore, require series doses to achieve sufficient immunity against pathogen. Here, we show that biomimetic mineralization inert model antigen, ovalbumin (OVA), in zeolitic imidazolate framework-8 (ZIF-8) significantly improves humoral immune response over three bolus OVA (OVA 3×). Encapsulation ZIF-8 (OVA@ZIF) demonstrated higher serum antibody titers 3×. OVA@ZIF vaccinated mice displayed populations germinal center (GC) B cells IgG1+ GC as opposed 3×, indicative class-switching recombination. We mechanism this phenomenon at least partly owed metalloimmunological effects zinc metal well sustained release composite. The system acts an antigen reservoir for antigen-presenting traffic into draining lymph node, enhancing response. Lastly, our produced quickly gram scale laboratory setting, up 20 000 vaccine doses.

Язык: Английский

Процитировано

11

β-Sitosterol targets ASS1 for Nrf2 ubiquitin-dependent degradation, inducing ROS-mediated apoptosis via the PTEN/PI3K/AKT signaling pathway in ovarian cancer DOI Creative Commons
Haoyu Wang, Jingchun Liu, Zihui Zhang

и другие.

Free Radical Biology and Medicine, Год журнала: 2024, Номер 214, С. 137 - 157

Опубликована: Фев. 15, 2024

The exploration of drugs derived from natural sources holds significant promise in addressing current limitations ovarian cancer (OC) treatments. While previous studies have highlighted the remarkable anti-cancer properties compound β-sitosterol (SIT) across various tumors, its specific role OC treatment remains unexplored. This study aims to investigate anti-tumor activity SIT using vitro and vivo models, delineate potential mechanisms, establish a preclinical theoretical foundation for future clinical trials, thus fostering further research. Utilizing network pharmacology, we pinpoint as promising candidate predict targets pathways. Through series experiments, unveil novel mechanism through which mitigates malignant biological behaviors cells by modulating redox status. Specifically, selectively argininosuccinate synthetase 1 (ASS1), protein markedly overexpressed tissues cells. Inhibiting ASS1, enhances interaction between Nrf2 Keap1, instigating ubiquitin-dependent degradation Nrf2, subsequently diminishing transcriptional activation downstream antioxidant genes HO-1 NQO1. interruption program results substantial accumulation reactive oxygen species (ROS) This, turn, upregulates PTEN, exerting negative regulation on phosphorylation AKT. suppression AKT signaling disrupted pathways associated with cell cycle, survival, apoptosis, migration, invasion, ultimately culminating death Our research uncovers new mechanisms against OC, contributing existing knowledge effects products context OC. Additionally, this unveils ASS1 regulating Nrf2-mediated governing homeostasis providing deeper understanding complex disease.

Язык: Английский

Процитировано

11

Human DNA topoisomerase I poisoning causes R loop–mediated genome instability attenuated by transcription factor IIS DOI Creative Commons
Renée C. Duardo, Jessica Marinello, Marco Russo

и другие.

Science Advances, Год журнала: 2024, Номер 10(21)

Опубликована: Май 24, 2024

DNA topoisomerase I can contribute to cancer genome instability. During catalytic activity, forms a transient intermediate, I–DNA cleavage complex (Top1cc) allow strand rotation and duplex relaxation, which lead elevated levels of DNA-RNA hybrids micronuclei. To comprehend the underlying mechanisms, we have integrated genomic data Top1cc-triggered double-strand breaks (DSBs) shortly after Top1cc induction, revealing that Top1ccs increase hybrid with different mechanisms. DSBs are at highly transcribed genes in early replicating initiation zones overlap downstream accumulated RNA polymerase II (RNAPII) gene 5′-ends. A transcription factor IIS mutant impairing elongation further increased RNAPII accumulation likely due backtracking. Moreover, trigger micronuclei when occurring during late G 1 or early/mid S, but not S. As transcription-replication conflicts attenuated by IIS, our results support role arrest Top1cc-induced leading

Язык: Английский

Процитировано

10

Nanoplastics from ground polyethylene terephthalate food containers: Genotoxicity in human lung epithelial A549 cells DOI Creative Commons
Mohammad Alzaben, Regīna Burve,

Katrin Loeschner

и другие.

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Год журнала: 2023, Номер 892, С. 503705 - 503705

Опубликована: Окт. 10, 2023

The ubiquitous pollution of plastic particles in most environmental matrices leads to concern about any potential adverse effects on human health. Most studies the toxicological effect nanoplastics has focused standard polystyrene. In reality humans are exposed a large variety different types and sizes material via oral intake inhalation. this study, we investigated polyethylene terephthalate (PET) nanoplastic from ground food containers supermarket. aim was investigate possible link between exposure PET genotoxic response cell model airway epithelial (A549) cells. Further, combined chemicals known alter cellular redox state, as partially compromised antioxidant defense system. DNA damage assessed by alkaline comet assay. have mean hydrodynamic diameter 136 nm water. results showed that led increased reactive oxygen species production (approximately 30 % increase compared unexposed cells). addition, level strand breaks (net = 0.10 lesions/106 base pair, 95 confidence interval: 0.01, 0.18 pair). Pre- or post-exposure hydrogen peroxide buthionine sulfoximine did not lead higher damage. Overall, study shows increases both intracellular A549

Язык: Английский

Процитировано

16

Isoliquiritigenin alleviates cerebral ischemia-reperfusion injury by reducing oxidative stress and ameliorating mitochondrial dysfunction via activating the Nrf2 pathway DOI Creative Commons

Xiaobing Lan,

Qing Wang, Yue Liu

и другие.

Redox Biology, Год журнала: 2024, Номер 77, С. 103406 - 103406

Опубликована: Окт. 22, 2024

Cerebral ischemia-reperfusion injury (CIRI) refers to a secondary brain that occurs when blood supply is restored ischemic tissue and one of the leading causes adult disability mortality. Multiple pathological mechanisms are involved in progression CIRI, including neuronal oxidative stress mitochondrial dysfunction. Isoliquiritigenin (ISL) has been preliminarily reported have potential neuroprotective effects on rats subjected cerebral insult. However, protective ISL not elucidated. This study aims further investigate ISL-mediated neuroprotection elucidate underlying molecular mechanism. The findings indicate treatment significantly alleviated middle artery occlusion (MCAO)-induced infarction, neurological deficits, histopathological damage, apoptosis mice. In vitro, effectively mitigated reduction cell viability, Na

Язык: Английский

Процитировано

7

Visualizing DNA single- and double-strand breaks in the Flash comet assay by DNA polymerase-assisted end-labelling DOI Creative Commons
Erik Bivehed, Björn Hellman, Leonie Wenson

и другие.

Nucleic Acids Research, Год журнала: 2024, Номер 52(4), С. e22 - e22

Опубликована: Янв. 23, 2024

Abstract In the comet assay, tails are formed after single-cell gel electrophoresis if cells have been exposed to genotoxic agents. These include a mixture of both DNA single-strand breaks (SSBs) and double-strand (DSBs). However, these two types strand cannot be distinguished using assay protocols with conventional stains. Since DSBs more problematic for cells, it would useful SSBs could differentially identified in same comet. order able distinguish between DSBs, we designed protocol polymerase-assisted damage analysis (PADDA) used combination Flash protocol, or on fixed cells. By polymerase I label terminal deoxynucleotidyl transferase fluorophore-labelled nucleotides. Herein, TK6-cells HaCat were either hydrogen peroxide (H2O2), ionising radiation (X-rays) cutting enzymes, then subjected followed by PADDA. PADDA offers wider detection range, unveiling previously undetected breaks.

Язык: Английский

Процитировано

6