Article
Oncology
Jiajing Niu, Jiamei Wang, Qi Zhang, Zhihua Zou, Yushuang Ding
Summary: The study revealed that sublethal doses of cinobufagin suppressed the viability of cancer cells by inducing oxidative stress, leading to DNA damage and cell cycle regulation that ultimately resulted in the induction of apoptosis.
CANCER CELL INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Shigeaki Sunada, Hiroko Saito, Doudou Zhang, Zeyu Xu, Yoshio Miki
Summary: CDK1 inhibitors regulate cellular sensitivity to DNA damage by controlling cell cycle progression and DNA repair inhibition, providing insights for developing clinical strategies targeting CDK1 inhibition in tumor cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Huan Liu, Wenchao Zhang, Lijie Jin, Shasha Liu, Liying Liang, Yanfei Wei
Summary: This study investigates the anticancer mechanism of Plumbagin (PLB) and its potential connections with oxidative stress, genotoxicity, and cell cycle arrest. The results indicate that PLB significantly inhibits HCC cell viability and colony formation, induces G2/M cell cycle arrest, oxidative stress, and DNA damage. These effects can be attenuated by NAC pretreatment. PLB triggers a DNA damage response by activating ATM, Chk1, Chk2, and p53. Furthermore, the key modulator of the G2/M transition factor, cdc25C, is downregulated in an ROS-dependent manner. Inhibition of the ATM-p53 pathway can reduce the occurrence of G2/M cell cycle arrest. Therefore, ROS-mediated oxidative stress plays a crucial role in PLB-induced G2/M cell cycle arrest mediated by the ATM-p53 pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Basudeb Das, Swapnil Sahoo, Bibekanand Mallick
Summary: This study reveals for the first time that HIWI2 acts as a tumor suppressor in fibrosarcoma by modulating the ROS/DNA damage/p53 pathway.
Article
Biochemistry & Molecular Biology
Jia-feng Tang, Guo-li Li, Tao Zhang, Yu-mei Du, Shi-ying Huang, Jian-hua Ran, Jing Li, Di-long Chen
Summary: In this study, it was found that HHT effectively inhibits the proliferation of melanoma cells by inducing DNA damage, apoptosis, and cell cycle arrest. Both in vitro and in vivo experiments confirmed the inhibitory effect of HHT on melanoma, providing evidence for its potential as an anti-melanoma agent.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Maria Gazdova, Radka Michalkova, Martin Kello, Maria Vilkova, Zuzana Kudlickova, Janette Baloghova, Ladislav Mirossay, Jan Mojzis
Summary: This study focused on investigating the antiproliferative effects of chalcone hybrids, particularly the chalcone-acridine hybrid 1C, in melanoma cancer cells. The study revealed that 1C exhibited potent antiproliferative effects by inducing cell cycle arrest and apoptosis. Additionally, the study found that 1C modulated the expression or phosphorylation of specific cell cycle-associated proteins and activated the DNA damage response pathway. Furthermore, 1C also induced apoptosis by causing mitochondrial dysfunction and activating caspase 3/7. The study suggests that the chalcone-acridine hybrid 1C may have potential as an antimelanoma agent in humans.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Abhipsha Dey, Martin Flajshans, Martin Psenicka, Ievgeniia Gazo
Summary: Embryogenesis is a crucial stage in an organism's life, but externally fertilizing species like fish are particularly vulnerable to DNA damage from environmental factors. While DNA repair pathways have been extensively studied in some fish species, there is a lack of knowledge about these processes in non-model aquaculture fish. This review aims to summarize the features of different DNA repair pathways during fish embryo development, including their regulation, roles in organogenesis, and response to genotoxic stress, to establish a connection between genotoxic stress and embryo phenotype.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Sneh M. Toprani, Dimitrios Bitounis, Qiansheng Huang, Nathalia Oliveira, Kee Woei Ng, Chor Yong Tay, Zachary D. Nagel, Philip Demokritou
Summary: The potential genotoxic effects of engineered nanomaterials (ENMs) on DNA repair pathways have been investigated using a fluorescence multiplex-host-cell reactivation (FM-HCR) assay. Results showed that some ENMs may enhance DNA repair capacity while others suppress it. This method can be a valuable part of a multitier, in vitro hazard assessment of ENMs, providing insights into the interplay between ENM properties, DNA repair efficiency, and genomic stability.
Article
Pharmacology & Pharmacy
Minjie Zhang, Jiaxi Qu, Zhiwei Gao, Qi Qi, Hong Yin, Ling Zhu, Yichen Wu, Wei Liu, Jian Yang, Xuefeng Huang
Summary: TAIII induces DNA damage and activates the ATM/Chk2 and p38 MAPK pathways, leading to G2/M phase arrest and apoptosis in breast cancer cells.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ireneusz Litwin, Seweryn Mucha, Ewa Pilarczyk, Robert Wysocki, Ewa Maciaszczyk-Dziubinska
Summary: In this study, it was found that trivalent antimony can cause various forms of DNA damage, including replication and oxidative DNA damage, and affect the activation of DNA damage checkpoints and formation of recombination repair centers in the model organism Saccharomyces cerevisiae.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Environmental Sciences
Binbin Wu, Yanling Zhang, Yuehua You, Yan Liang
Summary: This study investigated the genetic toxicity of chlorinated sediment hydrophobic organic compounds (HPOCs) from reservoirs along the Dongjiang River. The results showed that the hydrophilic organic compounds (Cl-HICs) were the major contributors to oxidative damage and dioxin-like toxicity compared to the hydrophobic organic compounds (Cl-HOCs). Antioxidants were found to significantly reduce the reactive oxygen species (ROS) induced by Cl-HOCs and Cl-HICs, but had little effect on DNA oxidative damage.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Plant Sciences
Asmita Pal, Soumee Sengupta, Rita Kundu
Summary: This study confirms the ethnopharmacological anticancer role of T. racemosa, inhibiting the abnormal proliferation of cervical cancer cells SiHa by inducing G2/M-phase cell cycle arrest and apoptotic cell death. Oxidative stress-mediated double-stranded DNA damage leads to apoptotic cell death through multiple routes, including the PI3K/Akt/NFKB pathway. The abundant alkaloid content of T. racemosa is suggested as the probable responsible cytotoxic principle.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ievgeniia Gazo, Roman Franek, Radek Sindelka, Ievgen Lebeda, Sahana Shivaramu, Martin Psenicka, Christoph Steinbach
Summary: Sterlet embryos show varying sensitivity to different genotoxicants, with some inducing DNA damage and activating DDR pathways, while others causing DNA damage without activating known DDR pathways, with effects also being stage-specific in embryo development. This study provides foundational information for future investigation of sterlet DDR pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jiyeon Leem, Jeong Su Oh
Summary: In this study, researchers discovered that MDC1 plays a non-canonical role in controlling G2/M transition in mouse oocytes by regulating APC/C-Cdh1-mediated cyclin B1 degradation in response to DNA damage. They also found that MDC1 depletion impairs spindle assembly by decreasing the integrity of microtubule organizing centers (MTOCs). These findings provide new insights into the regulation of the G2/M DNA damage checkpoint and cell cycle control in oocytes.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Environmental Sciences
Sonalin Rath, Surajit Das
Summary: Bacteria thriving in the mangrove ecosystem play a significant role in elemental cycles, but their performance is influenced by climate change and environmental stressors. This study investigates the genotoxic effect of such stressors on mangrove bacteria and their adaptation strategies. The results show cellular injuries and DNA damage in response to stressors, with different bacterial strains exhibiting varying levels of tolerance and adaptive mechanisms.
ENVIRONMENTAL POLLUTION
(2023)
Article
Neurosciences
Rashmi Joglekar, Marty Cauley, Taylor Lipsich, David L. Corcoran, Heather B. Patisaul, Edward D. Levin, Joel N. Meyer, Margaret M. McCarthy, Susan K. Murphy
Summary: Nicotine exposure during development may affect the sexual differentiation of the developing brain, potentially influencing adult sexual behavior in rodents. This study found that developmental nicotine exposure had an impact on the sexual differentiation of the preoptic area (POA) in rats, with the normal sex differences in male sexual behavior and POA area eliminated in nicotine-treated animals. In neonates, nicotine exposure also induced changes in gene expression and DNA methylation levels at sexually-dimorphic regions, suggesting the involvement of epigenetic mechanisms in the masculinization of the rat POA.
Article
Multidisciplinary Sciences
Silvia Maglioni, Alfonso Schiavi, Marlen Melcher, Vanessa Brinkmann, Zhongrui Luo, Anna Laromaine, Nuno Raimundo, Joel N. Meyer, Felix Distelmaier, Natascia Ventura
Summary: Complex-I deficiency is the most common cause of human mitochondriopathies. Therapeutic options are currently lacking due to the limited model systems. In this study, researchers used C. elegans models to study these diseases and found that the natural compound lutein can prevent neurodevelopmental deficits, pointing to a potential therapeutic target for human diseases.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Tess C. Leuthner, Laura Benzing, Brendan F. Kohrn, Christina M. Bergemann, Michael J. Hipp, Kathleen A. Hershberger, Danielle F. Mello, Tymofii Sokolskyi, Kevin Stevenson, Ilaria R. Merutka, Sarah A. Seay, Simon G. Gregory, Scott R. Kennedy, Joel N. Meyer
Summary: Mitochondrial DNA is prone to mutation, but the processes that regulate mtDNA mutation are not fully understood. In Caenorhabditis elegans, we found widespread mtDNA heteroplasmy and identified C:G -> A:T mutations, which are associated with oxidative damage, as the dominant form of mtDNA mutation. Exposure to two nuclear genome mutagens did not affect mtDNA mutation frequency or spectrum, but significantly increased nuclear mutation rate. Mutants with defective mitophagy accumulated higher levels of mtDNA damage but had only small differences in mtDNA mutation compared to wild-type. These findings suggest the existence of additional mechanisms that regulate mtDNA mutation across generations.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Genetics & Heredity
Liliana Elizabeth Rodriguez-Salgado, Claudia Tamar Silva-Aldana, Esteban Medina-Mendez, Jose Bareno-Silva, Mauricio Arcos-Burgos, Daniel Felipe Silgado-Guzman, Carlos M. Restrepo
Summary: This study aimed to determine the prevalence of secondary findings (SF) in a Colombian population for 59 genes associated with 27 genetic diseases. The results showed that 8.13% of patients had pathogenic variants in 11 genes. No association was found between socio-demographic variables and the need to report SF. This study provides the first approach to the spectrum of actionable pathogenic variants in the Colombian population.
Article
Multidisciplinary Sciences
Oscar M. Vidal, Jorge I. Velez, Mauricio Arcos-Burgos
Summary: Attention deficit/hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder. This study examined the impact of non-synonymous SNPs in the ADGRL3 gene on ADHD development. The findings suggest that these mutations disrupt the normal structure of ADGRL3 and may affect its metabolic regulation, potentially linking ADHD to the pathogenesis of diabetes mellitus.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
M. Daniela Velez, Maria A. Llano-Ramirez, Carolina Ramon, Jessica Rojas, Carolina Bedoya, Sandra Arango-Varela, Gloria A. Santa-Gonzalex, Maritza Gil
Summary: An ultrasound-assisted extraction was conducted to obtain a crude extract with antioxidant properties from organically grown Isabella grapes in Antioquia, Colombia. The extract showed high levels of polyphenols and exhibited biological effects on breast cancer cells, making it a potential adjuvant chemopreventive agent for breast cancer treatment.
Article
Genetics & Heredity
Yina D. Carrillo, Paula Rueda-Gaitan, Orlando Gualdron, Carlos Estrada-Serrato, Taryn A. Castro-Cuesta, Olga Londono, Luna Rodriguez-Salazar, Mario Isaza-Ruget, Mauricio Arcos-Burgos, Juan Javier Lopez Rivera
Summary: Copy number variants (CNVs) are a major cause of neurodevelopmental delay and congenital malformations, and chromosomal microarray analysis (CMA) is the gold standard for molecular characterization of CNVs. We applied CMA in the clinical diagnostic process of patients as requested by their medical provider. Among 3380 patients, we identified 830 CNVs with potential clinical significance, and 10.6% of them were most likely the final cause of the patients' clinical phenotype. The rate of pathogenic or likely pathogenic findings among patients with CNVs was 60.75% for neurodevelopmental phenotypes and 59% for epileptic phenotypes.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Marine & Freshwater Biology
Jordan S. Kozal, Nishad Jayasundara, Andrey Massarsky, Casey D. Lindberg, Anthony N. Oliveri, Ellen M. Cooper, Edward D. Levin, Joel N. Meyer, Richard T. Di Giulio
Summary: This study evaluated the role of mitochondria in the cross-generational toxicity of benzo(a)pyrene and found significant mitochondrial impairments in offspring caused by maternal exposure.
AQUATIC TOXICOLOGY
(2023)
Article
Environmental Sciences
Laura C. Palacio, Geraldine Durango-Giraldo, Camilo Zapata-Hernandez, Gloria A. Santa-Gonzalez, Diego Uribe, Javier Saiz, Robison Buitrago-Sierra, Catalina Tobon
Summary: This study analyzed the physicochemical properties of particulate matter (PM) collected from different areas in the Metropolitan Area of Aburra Valley in Colombia. The results showed that the composition of PM varied based on the socioeconomic dynamics specific to each city. The study also found that PM had toxic effects on human health and could potentially contribute to the development of cardiac arrhythmias.
ENVIRONMENTAL POLLUTION
(2023)
Article
Multidisciplinary Sciences
M. Daniela Velez, Johanna Pedroza-Diaz, Gloria A. Santa-Gonzalez
Summary: Functional foods with bioactive compounds have chemopreventive potential and are of interest in cancer research, particularly for colorectal cancer. Chlorogenic acid, a phenolic compound, has been found to exhibit cytotoxic effects on colorectal adenocarcinoma cells and modulate the Wnt-/beta-catenin pathway.
Article
Chemistry, Analytical
Pooja Lalwani, Dillon E. King, Katherine S. Morton, Nelson A. Rivera Jr, Javier Huayta, Heileen Hsu-Kim, Joel N. Meyer
Summary: Lead is a developmental toxicant that can enter mitochondria through the mitochondrial calcium uniporter. In this study, we developed mechanism-based hypotheses about the interactive effects of lead with other mitochondria-damaging chemicals and tested these hypotheses using human liver cells. The results showed that the combination of lead, FCCP, and RuRed significantly decreased cell viability, suggesting an interactive toxicity. Further analysis ruled out altered cellular uptake and membrane potential as the mechanisms for this toxicity.
ENVIRONMENTAL SCIENCE-PROCESSES & IMPACTS
(2023)
Article
Multidisciplinary Sciences
Andrew S. Clark, Zachary Kalmanson, Katherine Morton, Jessica Hartman, Joel Meyer, Adriana San-Miguel
Summary: We developed an automated, unbiased image processing algorithm to quantify dopaminergic neurodegeneration in C. elegans, which can be used on images acquired with different microscopy setups. Our platform was validated by detecting and quantifying neurodegeneration in nematodes exposed to different stressors. The algorithm accurately detected 20 different metrics of neurodegeneration and provided comparative insights into how each exposure affects dopaminergic neurodegeneration patterns.
Meeting Abstract
Environmental Sciences
Javier Huayta, Joel N. Meyer
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2023)
Article
Marine & Freshwater Biology
Jordan S. Kozal, Nishad Jayasundara, Andrey Massarsky, Casey D. Lindberg, Anthony N. Oliveri, Ellen M. Cooper, Edward D. Levin, Joel N. Meyer, Richard T. Di Giulio
Summary: The potential adverse effects of polycyclic aromatic hydrocarbons (PAHs) on human and wildlife health, particularly across generations, have become a concern. This study found that exposure to benzo(a)pyrene (BaP), a model PAH and mitochondrial toxicant, led to altered mitochondrial function and metabolic partitioning in zebrafish embryos. These effects occurred in offspring largely independent of maternal effects on ovaries, suggesting that PAH-induced mitochondrial dysfunction may manifest in subsequent generations.
AQUATIC TOXICOLOGY
(2023)
Meeting Abstract
Environmental Sciences
Dillon King, A. Clare Sparling, Dillon Lloyd, Matthew J. Satusky, Mackenzie Martinez, Carole Grenier, Christina Bergemann, Rachel Maguire, Cathrine Hoyo, Joel N. Meyer, Susan K. Murphy
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2022)