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Molecular Microbiology Jan 2024Free-living organisms frequently encounter unfavorable abiotic environmental factors. Those who adapt and cope with sudden changes in the external environment survive.... (Review)
Review
Free-living organisms frequently encounter unfavorable abiotic environmental factors. Those who adapt and cope with sudden changes in the external environment survive. Desiccation is one of the most common and frequently encountered stresses in nature. On the contrary, ionizing radiations are limited to high local concentrations of naturally occurring radioactive materials and related anthropogenic activities. Yet, resistance to high doses of ionizing radiation is evident across the tree of life. The evolution of desiccation resistance has been linked to the evolution of ionizing radiation resistance, although, evidence to support the idea that the evolution of desiccation tolerance is a necessary precursor to ionizing radiation resistance is lacking. Moreover, the presence of radioresistance in hyperthermophiles suggests multiple paths lead to radiation resistance. In this minireview, we focus on the molecular aspects of damage dynamics and damage response pathways comprising protective and restorative functions with a definitive survival advantage, to explore the serendipitous genesis of ionizing radiation resistance.
Topics: Radiation, Ionizing; Deinococcus; Radiation Tolerance; DNA Repair
PubMed: 38082498
DOI: 10.1111/mmi.15208 -
International Review of Cell and... 2024Radiation therapy is a cornerstone of modern cancer treatment. Treatment is based on depositing focal radiation to the tumor to inhibit cell growth, proliferation and... (Review)
Review
Radiation therapy is a cornerstone of modern cancer treatment. Treatment is based on depositing focal radiation to the tumor to inhibit cell growth, proliferation and metastasis, and to promote the death of cancer cells. In addition, radiation also affects non-tumor cells in the tumor microenvironmental (TME). Radiation resistance of the tumor cells is the most common cause of treatment failure, allowing survival of cancer cell and subsequent tumor growing. Molecular radioresistance comprises genetic and epigenetic characteristics inherent in cancer cells, or characteristics acquired after exposure to radiation. Furthermore, cancer stem cells (CSCs) and non-tumor cells into the TME as stromal and immune cells have a role in promoting and maintaining radioresistant tumor phenotypes. Different regulatory molecules and pathways distinctive of radiation resistance include DNA repair, survival signaling and cell death pathways. Epigenetic mechanisms are one of the most relevant events that occur after radiotherapy to regulate the expression and function of key genes and proteins in the differential radiation-response. This article reviews recent data on the main molecular mechanisms and signaling pathways related to the biological response to radiotherapy in cancer; highlighting the epigenetic control exerted by DNA methylation, histone marks, chromatin remodeling and m6A RNA methylation on gene expression and activation of signaling pathways related to radiation therapy response.
Topics: Humans; Radiation Tolerance; Neoplasms; Epigenesis, Genetic; DNA Methylation; DNA Repair
PubMed: 38359968
DOI: 10.1016/bs.ircmb.2023.07.008 -
Fungal Biology Dec 2023We investigated conidial mass production of eight isolates of six entomopathogenic fungi (EPF), Aphanocladium album (ARSEF 1329), Beauveria bassiana (ARSEF 252 and...
We investigated conidial mass production of eight isolates of six entomopathogenic fungi (EPF), Aphanocladium album (ARSEF 1329), Beauveria bassiana (ARSEF 252 and 3462), Lecanicillium aphanocladii (ARSEF 6433), Metarhizium anisopliae sensu lato (ARSEF 2341), Metarhizium pingshaense (ARSEF 1545), and Simplicillium lanosoniveum (ARSEF 6430 and 6651) on white or brown rice at four moisture conditions (75-100%). The tolerance of mass-produced conidia of the eight fungal isolates to UV-B radiation and heat (45 °C) were also evaluated. For each moisture content compared, a 20-g sample of rice in a polypropylene bag was inoculated with each fungal isolate in three replicates and incubated at 28 ± 1 °C for 14 days. Conidia were then harvested by washing the substrate, and conidial concentrations determined by haemocytometer counts. Conidial suspensions were inoculated on PDAY with 0.002% benomyl in Petri plates and exposed to 978 mW m of Quaite-weighted UV-B for 2 h. Additionally, conidial suspensions were exposed to 45 °C for 3 h, and aliquots inoculated on PDAY with benomyl. The plates were incubated at 28 ± 1 °C, and germination was assessed at 400 × magnification after 48 h. Conidial production was generally higher on white rice than on brown rice for all fungal species, except for L. aphanocladii ARSEF 6433, regardless of moisture combinations. The 100% moisture condition provided higher conidial production for B. bassiana (ARSEF 252 and ARSEF 3462) and M. anisopliae (ARSEF 2341) isolates, while the addition of 10% peanut oil enhanced conidial yield for S. lanosoniveum isolate ARSEF 6430. B. bassiana ARSEF 3462 on white rice with 100% water yielded the highest conidial production (approximately 1.3 × 10 conidia g of substrate). Conidia produced on white rice with the different moisture conditions did not differ in tolerance to UV-B radiation or heat. However, high tolerance to UV-B radiation and heat was observed for B. bassiana, M. anisopliae, and A. album isolates. Heat-treated conidia of S. lanosoniveum and L. aphanocladii did not germinate.
Topics: Spores, Fungal; Hot Temperature; Benomyl; Metarhizium; Beauveria; Pest Control, Biological
PubMed: 38097326
DOI: 10.1016/j.funbio.2023.07.001 -
BioRxiv : the Preprint Server For... Aug 2023Understanding how and when key novel adaptations evolved is a central goal of evolutionary biology. Within the radiation of , many mushroom-feeding species are...
Understanding how and when key novel adaptations evolved is a central goal of evolutionary biology. Within the radiation of , many mushroom-feeding species are tolerant of host toxins, such as cyclopeptides, that are lethal to nearly all other eukaryotes. In this study, we used phylogenetic and functional approaches to investigate the evolution of cyclopeptide tolerance in the radiation of . We first inferred the evolutionary relationships among 48 species in this radiation using 978 single copy orthologs. Our results resolved previous incongruities within species groups across the phylogeny. Second, we expanded on previous studies of toxin tolerance by assaying 16 of these species for tolerance to α-amanitin and found that six of these species could develop on diet with toxin. Third, we examined fly development on a diet containing a natural mix of toxins extracted from the Death Cap mushroom. Both tolerant and susceptible species developed on diet with this mix, though tolerant species survived at significantly higher concentrations. Finally, we asked how cyclopeptide tolerance might have evolved across the radiation and inferred that toxin tolerance was ancestral and subsequently lost multiple times. Our results suggest the evolutionary history of cyclopeptide tolerance is complex, and simply describing this trait as present or absent does not fully capture the occurrence or impact on this adaptive radiation. More broadly, the evolution of novelty can be more complex than previously thought, and that accurate descriptions of such novelties are critical in studies examining their evolution.
PubMed: 37577671
DOI: 10.1101/2023.08.03.551872 -
Journal of Cancer Research and Clinical... Jan 2024Mitochondria are organelles with double-membrane structure of inner and outer membrane, which provides main energy support for cell growth and metabolism. Reactive... (Review)
Review
Mitochondria are organelles with double-membrane structure of inner and outer membrane, which provides main energy support for cell growth and metabolism. Reactive oxygen species (ROS) mainly comes from mitochondrial and can cause irreversible damage to cells under oxidative stress. Thus, mitochondrial homeostasis is the basis for maintaining the normal physiological function of cells and mitophagy plays a pivotal role in the maintenance of mitochondrial homeostasis. At present, to enhance the sensitivity of cancer cells to radiotherapy and chemotherapy by regulating mitochondria has increasingly become a hot spot of cancer therapy. It is particularly important to study the effect of ionizing radiation (IR) on mitochondria and the role of mitophagy in the radiosensitivity of cancer cells. Most of the existing reviews have focused on mitophagy-related molecules or pathways and the impact of mitophagy on diseases. In this review, we mainly focus on discussing the relationship between mitophagy and radiosensitivity of cancer cells around mitochondria and IR.
Topics: Humans; Mitophagy; Mitochondria; Oxidative Stress; Reactive Oxygen Species; Radiation Tolerance; Neoplasms
PubMed: 38238458
DOI: 10.1007/s00432-023-05515-2 -
Journal of Clinical Oncology : Official... Aug 2023Radiation-associated cardiac disease is a major cause of morbidity/mortality among childhood cancer survivors. Radiation dose-response relationships for cardiac...
PURPOSE
Radiation-associated cardiac disease is a major cause of morbidity/mortality among childhood cancer survivors. Radiation dose-response relationships for cardiac substructures and cardiac diseases remain unestablished.
METHODS
Using the 25,481 5-year survivors of childhood cancer treated from 1970 to 1999 in the Childhood Cancer Survivor Study, we evaluated coronary artery disease (CAD), heart failure (HF), valvular disease (VD), and arrhythmia. We reconstructed radiation doses for each survivor to the coronary arteries, chambers, valves, and whole heart. Excess relative rate (ERR) models and piecewise exponential models evaluated dose-response relationships.
RESULTS
The cumulative incidence 35 years from diagnosis was 3.9% (95% CI, 3.4 to 4.3) for CAD, 3.8% (95% CI, 3.4 to 4.2) for HF, 1.2% (95% CI, 1.0 to 1.5) for VD, and 1.4% (95% CI, 1.1 to 1.6) for arrhythmia. A total of 12,288 survivors (48.2%) were exposed to radiotherapy. Quadratic ERR models improved fit compared with linear ERR models for the dose-response relationship between mean whole heart and CAD, HF, and arrhythmia, suggesting a potential threshold dose; however, such departure from linearity was not observed for most cardiac substructure end point dose-response relationships. Mean doses of 5-9.9 Gy to the whole heart did not increase the risk of any cardiac diseases. Mean doses of 5-9.9 Gy to the right coronary artery (rate ratio [RR], 2.6 [95% CI, 1.6 to 4.1]) and left ventricle (RR, 2.2 [95% CI, 1.3 to 3.7]) increased risk of CAD, and to the tricuspid valve (RR, 5.5 [95% CI, 2.0 to 15.1]) and right ventricle (RR, 8.4 [95% CI, 3.7 to 19.0]) increased risk of VD.
CONCLUSION
Among children with cancer, there may be no threshold dose below which radiation to the cardiac substructures does not increase the risk of cardiac diseases. This emphasizes their importance in modern treatment planning.
Topics: Child; Humans; Neoplasms; Cancer Survivors; Survivors; Heart Diseases; Radiation Injuries; Dose-Response Relationship, Radiation; Heart Failure
PubMed: 37307512
DOI: 10.1200/JCO.22.02320 -
The Science of the Total Environment Mar 2024Adaptation to environmental stressors is an essential property of plants that allows them, despite an immobile lifestyle, to survive in a changeable environment. The... (Review)
Review
Adaptation to environmental stressors is an essential property of plants that allows them, despite an immobile lifestyle, to survive in a changeable environment. The chain of successive events culminating in the final radiobiological reaction begins with the absorption of energy of ionizing radiation in the cell. Starting from stochastic acts of molecular injury formation, radiation damage gradually acquires deterministic features, which are expressed in a limited number of phenomena that complete plant radiation damage. As plants undergo specialization, the differences between plants and animals become more pronounced, leading to distinct responses to radiation. Chronic radiation exposure may activate biological mechanisms resulting in increased radioresistance of the population. The higher the level of radiation exposure and the sensitivity of plants to radiation, the more intensive the selection. Depending on the circumstances, enhanced radioresistance of a population can be achieved in different ways or has not evolved at all. High dose rates of chronic irradiation leаd to selection for the efficiency of repair systems, while low dose rates activate epigenetic mechanisms that lead to the maintenance of oxidative balance, additional synthesis of chaperones, and control of TEs transposition. Due to huge differences in the radiosensitivity of organisms that make up the ecosystem, irradiation can result in disruption of connections between components of ecosystems which may lead to consequences that can differ drastically from those expected at the organismal and population levels. Therefore, the use of ecological knowledge is essential for understanding the responses of populations and ecosystems to radiation exposure.
Topics: Animals; Ecosystem; Radiation, Ionizing; Radiation Tolerance; Epigenesis, Genetic
PubMed: 38246389
DOI: 10.1016/j.scitotenv.2024.170201 -
Ecotoxicology and Environmental Safety Aug 2023Ultraviolet B (UV-B, 280-320 nm) radiation is a major environmental stressor for aquatic organisms on Earth's surface. Its effects on biological systems are well known,...
Ultraviolet B (UV-B, 280-320 nm) radiation is a major environmental stressor for aquatic organisms on Earth's surface. Its effects on biological systems are well known, but the mechanisms by which organisms respond and adapt to UV-B radiation are still being explored. In this study, we investigated the effects of UV-B radiation on the monogonont rotifer Brachionus asplanchnoidis, focusing on physiological parameters, antioxidant systems, DNA damage, and DNA repair-related molecular mechanism. Our results showed that the LD was at 28.53 kJ/m, indicating strong tolerance to UV-B. However, UV-B radiation caused adverse effects on growth and reproduction, with shortened reproductive period and longevity, decreased fecundity and hatchability, and inhibition of population growth. Biochemical analyses revealed severe oxidative damage and lipid peroxidation, with increased ROS and MDA levels. Activities of antioxidant enzymes were highly induced at low doses but decreased at high doses. DNA damage also occurred in UV-B-exposed rotifers. Furthermore, selected DNA repair-related genes were up-regulated in a dose-dependent manner. These findings provide a comprehensive understanding of the effects of UV-B radiation on rotifers and highlight the importance of considering both ecological and molecular responses in assessing the impact of UV-B radiation on aquatic organisms.
PubMed: 37542982
DOI: 10.1016/j.ecoenv.2023.115319 -
Oral Oncology Nov 2023Although human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) patients typically experience excellent survival, 15-20 % of patients recur...
OBJECTIVES
Although human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) patients typically experience excellent survival, 15-20 % of patients recur after treatment with chemotherapy and radiation. Therefore, there is a need for biomarkers of treatment failure to guide treatment intensity.
MATERIALS AND METHODS
Whole genome sequencing was carried out on HPV+OPSCC patients who were primarily treated with concurrent chemotherapy (cisplatin) and radiation. We then explored whether the loss of LRP1Bwas sufficient to drive an aggressive phenotype, and promote a resistance to cisplatin and radiation therapy both in vitro using HPV+ cell lines (93VU147T, UMSCC47, UWO37 and UWO23) and in vivo.
RESULTS
Through integrative genomic analysis of three HPV+OPSCC tumour datasets, we identified that deletion of LRP1B was enriched in samples that recurred following chemo-radiation. Knockdown using siRNA in four HPV+ cell lines (UWO23, UWO37, UMSCC47 and 93VU147T) resulted in increased proliferation of all cases. CRISPR/Cas9 deletion of LRP1B in the same cell line panel demonstrated increased proliferation, clonogenic growth and migration, as well as resistance to both cisplatin and radiation in LRP1B deleted cells compared to their respective non-targeting control cells. Cell line derived xenograft studies indicated that the LRP1B knockout tumours were more resistant to cisplatin and radiation therapy compared to their controls invivo.
CONCLUSION
Taken together, our work implicates LRP1B deletion as a potential biomarker for identifying treatment resistant HPV+ OPSCC cases.
Topics: Humans; Carcinoma, Squamous Cell; Cisplatin; Head and Neck Neoplasms; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Papillomavirus Infections; Receptors, LDL; Squamous Cell Carcinoma of Head and Neck; Drug Resistance, Neoplasm; Radiation Tolerance
PubMed: 37778229
DOI: 10.1016/j.oraloncology.2023.106580 -
A tRF-5a fragment that regulates radiation resistance of colorectal cancer cells by targeting MKNK1.Journal of Cellular and Molecular... Dec 2023Radiotherapy serves as a crucial strategy in the treatment of colorectal cancer (CRC). However, its efficacy is often hindered by the challenge of radiation resistance....
Radiotherapy serves as a crucial strategy in the treatment of colorectal cancer (CRC). However, its efficacy is often hindered by the challenge of radiation resistance. Although the literature suggests that some tRNA-derived small RNAs (tsRNAs) are associated with various cancers, studies reporting the relationship of tsRNAs with cancer cell radiosensitivity have not been published yet. In our study, we utilized tsRNAs sequencing to predict differentially expressed tsRNAs in two CRC cells and their radioresistant cells, and 10 tsRNAs with significant differences in expression were validated by qPCR. The target genes of tRF-16-7X9PN5D were predicted and verified by the bioinformatics, dual-luciferase reporter gene assay and western blotting analyses. Wound healing, colony formation, transwell invasion and CCK-8 assays were performed to detect the effects of tRF-16-7X9PN5D on cell function and radiosensitivity. Western blotting evaluated the relationship between tRF-16-7X9PN5D and the MKNK-eIF4E axis. Our findings demonstrated that tRF-16-7X9PN5D expression was substantially downregulated in radioresistant CRC cells. Furthermore, tRF-16-7X9PN5D could promote CRC cells' ability to proliferate, migrate, invade and obtain radiation resistance by targeting MKNK1. Finally, tRF-16-7X9PN5D could regulate eIF4E phosphorylation via MKNK1. This investigation indicated that tRF-16-7X9PN5D has an essential regulatory role in the radiation resistance of CRC by directly targeting MKNK1, and may be a new pathway for regulating the CRC radiosensitivity.
Topics: Humans; Biological Assay; Colorectal Neoplasms; Eukaryotic Initiation Factor-4E; Genes, Reporter; Intracellular Signaling Peptides and Proteins; Phosphorylation; Protein Serine-Threonine Kinases; Radiation Tolerance
PubMed: 37864471
DOI: 10.1111/jcmm.17982