Search Results (16)

Low-dose ionizing radiation (LDIR) is a prevalent environmental factor with profound impacts on male reproductive health, particularly on the testicular immune microenvironment. This review examines the multifaceted effects of LDIR, emphasizing its ability to induce genotoxic stress, oxidative damage, and epigenetic modifications in reproductive cells. These alterations compromise DNA repair, disrupt chromatin structure, and induce immune dysregulation. Immune cells such as macrophages, T cells, natural killer cells, and dendritic cells exhibit significant functional changes under LDIR exposure, destabilizing the immune privilege critical for normal spermatogenesis. The long-term health implications of LDIR include impaired sperm quality, reduced fertility, and transgenerational risks through heritable genomic instability. This review underscores the importance of exploring the mechanisms underlying immune dysregulation and developing effective protective strategies. While LDIR’s full impact on male reproductive health remains to be elucidated, addressing the gaps in our understanding of immune microenvironmental changes is crucial for mitigating its adverse effects and improving reproductive health outcomes. Full article

High doses of ionizing radiation (HDIR) are known to induce cellular damage, whereas low-dose ionizing radiation (LDIR) may trigger protective biological responses. Recent studies have explored the potential benefits of LDIR in treating diabetes and its complications. However, the direct effects of LDIR on pancreatic β-cells and the underlying mechanisms remain to be elucidated. This study aimed to evaluate the effects of LDIR on pancreatic β-cell functionality and elucidate the underlying molecular mechanisms involved. Rat RIN-m5F cells were exposed to LDIR (25 mGy) or HDIR (2.5 Gy) to examine changes in insulin mRNA expression, secretion, DNA damage, and apoptosis. The roles of reactive oxygen species (ROS) and the p38 mitogen-activated protein kinase (MAPK) pathway were assessed via the use of antioxidants and pathway inhibitors. The findings indicated that LDIR transiently increased both insulin synthesis and secretion without inducing apoptosis or affecting cell proliferation. In contrast, HDIR induced a significant increase in apoptosis and a marked inhibition of proliferation. LDIR was observed to temporarily increase ROS production, activating the p38 MAPK pathway and facilitating insulin synthesis via the upregulation of PDX-1. Notably, LDIR did not induce DNA double-strand breaks or activate the ATM-dependent DNA repair pathways, unlike HDIR, which induced apoptosis through overactivation of the ROS/p38 MAPK pathway. In conclusion, LDIR enhanced pancreatic β-cell functionality via ROS-mediated activation of the p38 MAPK pathway, highlighting its potential therapeutic applications in diabetes management. Full article

Background/Objectives: With technological development, ionizing radiation has found applications in numerous occupations. However, the determination and quantification of the damage resulting from exposure to it remains rather unclear, along with the damage to particular organs. The aim of this systematic review was to investigate the relationship between low-dose ionizing radiation (LDIR) in exposed workers and possible functional changes and cancer development in the thyroid gland. Methods: We included observational studies evidencing the correlation under study. Data extraction and analysis was conducted on all included studies. The research strategy included three electronic databases (PubMed, Scopus, and Web of Science). The systematic review followed PRISMA guidelines, and the research protocol was submitted to PROSPERO (CRD:42023425839). Results: The search initially yielded 166 articles and, once duplicates and irrelevant articles were removed, a total of 15 useful articles were reviewed. Qualitative analysis of the studies showed that the TSH value does not change following exposure, while a reduction in fT3 and an increase or reduction in fT4 can be observed. Furthermore, the correlation between thyroid cancer and occupational exposure to radiation was not shown with certainty, but there was some evidence of increased gland volume and nodule formation. Conclusions: Even at low doses, ionizing radiation adversely affects thyroid activity. In this regard, new studies should be carried out in order to further investigate and define this issue and, consequently, outline useful measures to ensure the protection of workers in contact with this particular physical agent. Full article

Background/Objectives: Low-dose ionizing radiation (LDIR) is commonly used in medical diagnoses and certain professions, but its long-term effects on noncancer diseases, particularly cardiovascular disease (CVD), remain uncertain. While LDIR has recognized diagnostic benefits, its influence on CVD mortality and disease progression is still debated, with some suggesting that low doses may even have beneficial effects, as per the hormesis theory. Methods: This meta-analysis aimed to evaluate the impact of LDIR on cardiovascular health outcomes. The study followed a systematic approach, using the PRISMA guidelines to select and analyze relevant studies from databases such as PubMed, Scopus, Web of Science, and Embase. Out of 167 identified studies, 8 were chosen for analysis, including 6 cohort studies and 2 experimental studies. Results: The findings indicated a significant link between LDIR exposure and increased CVD mortality and progression, though some studies also noted potential benefits of LDIR in certain conditions, aligning with the hormesis theory. Conclusions: These mixed results raise questions about the specific conditions under which LDIR might be beneficial or harmful. Overall, the study emphasizes the need for strict radiation control measures and health monitoring for individuals regularly exposed to LDIR, both in clinical and occupational settings. Full article

Although ionizing radiation (IR) is widely used for therapeutic and research purposes, studies on low-dose ionizing radiation (LDIR) are limited compared with those on other IR approaches, such as high-dose gamma irradiation and ultraviolet irradiation. High-dose IR affects DNA damage response and nucleotide–protein crosslinking, among other processes; however, the molecular consequences of LDIR have been poorly investigated. Here, we developed a method to profile RNA species crosslinked to an RNA-binding protein, namely, human antigen R (HuR), using LDIR and high-throughput RNA sequencing. The RNA fragments isolated via LDIR-crosslinking and immunoprecipitation sequencing were crosslinked to HuR and protected from RNase-mediated digestion. Upon crosslinking HuR to target mRNAs such as PAX6, ZFP91, NR2F6, and CAND2, the transcripts degraded rapidly in human cell lines. Additionally, PAX6 and NR2F6 downregulation mediated the beneficial effects of LDIR on cell viability. Thus, our approach provides a method for investigating post-transcriptional gene regulation using LDIR. Full article

Each person is inevitably exposed to low doses of ionizing radiation (LDIR) throughout their life. The research results of LDIR effects are ambiguous and an accurate assessment of the risks associated with the influence of LDIR is an important task. Mesenchymal stromal cells (MSCs) are the regenerative reserve of an adult organism; because of this, they are a promising model for studying the effects of LDIR. The qualitative and quantitative changes in their characteristics can also be considered promising criteria for assessing the risks of LDIR exposure. The MSCs from human connective gingiva tissue (hG-MSCs) were irradiated at doses of 50, 100, 250, and 1000 mGy by the X-ray unit RUST-M1 (Russia). The cells were cultured continuously for 64 days after irradiation. During the study, we evaluated the secretory profile of hG-MSCs (IL-10, IDO, IL-6, IL-8, VEGF-A) using an ELISA test, the immunophenotype (CD45, CD34, CD90, CD105, CD73, HLA-DR, CD44) using flow cytometry, and the proliferative activity using the xCelligence RTCA cell analyzer at the chosen time points. The results of study have indicated the development of stimulating effects in the early stages of cultivation after irradiation using low doses of X-ray radiation. On the contrary, the effects of the low doses were comparable with the effects of medium doses of X-ray radiation in the long-term periods of cultivation after irradiation and have indicated the inhibition of the functional activity of MSCs. Full article

There is significant interest in the response of the mammalian brain to low-dose ionizing radiation (LDIR), mainly examined by gene or protein expression, with applications in radiation safety on Earth, the atmosphere and outer space. Potential associations of molecular-level responses with sensory or cognitive defects and neurodegenerative diseases are currently under investigation. Previously, we have described a light-weight approach for the storage, analysis and distribution of relevant datasets, with the platform BRIDE. We have re-implemented the platform as BRIDE v2 on the cloud, using the bioinformatics infrastructure ELIXIR. We connected the annotated list of 3174 unique gene records with modern omics resources for downstream computational analysis. BRIDE v2 is a cloud-based platform with capabilities that enable researchers to extract, analyze, visualize as well as export the gene collection. The resource is freely available online at <http://bride-db.eu>. Full article

Cells exposed to ionizing radiation undergo a series of complex responses, including DNA damage, reproductive cell death, and altered proliferation states, which are all linked to cell cycle dynamics. For many years, a great deal of research has been conducted on cell cycle checkpoints and their regulators in mammalian cells in response to high-dose exposures to ionizing radiation. However, it is unclear how low-dose ionizing radiation (LDIR) regulates the cell cycle progression. A growing body of evidence demonstrates that LDIR may have profound effects on cellular functions. In this review, we summarize the current understanding of how LDIR (of up to 200 mGy) regulates the cell cycle and cell-cycle-associated proteins in various cellular settings. In light of current findings, we also illustrate the conceptual function and possible dichotomous role of p21^Waf1, a transcriptional target of p53, in response to LDIR. Full article

The concept of hormesis describes a phenomenon of adaptive response to low-dose ionizing radiation (LDIR). Similarly, the concept of mitohormesis states that the adaptive program in mitochondria is activated in response to minor stress effects. The mechanisms of hormesis effects are not clear, but it is assumed that they can be mediated by reactive oxygen species. Here, we studied effects of LDIR on mitochondria in mesenchymal stem cells. We have found that X-ray radiation at a dose of 10 cGy as well as oxidized fragments of cell-free DNA (cfDNA) at a concentration of 50 ng/mL resulted in an increased expression of a large number of genes regulating the function of the mitochondrial respiratory chain complexes in human mesenchymal stem cells (MSC). Several genes remained upregulated within hours after the exposure. Both X-ray radiation and oxidized cfDNA resulted in upregulation of FIS1 and MFN1 genes, which regulated fusion and fission of mitochondria, within 3–24 h after the exposure. Three hours after the exposure, the number of copies of mitochondrial DNA in cells had increased. These findings support the hypothesis that assumes oxidized cell-free DNA as a mediator of MSC response to low doses of radiation. Full article

The purpose of this study was to evaluate the relationship between blood redox status, dose and antioxidant dietary intake of different hospital staff groups exposed to low doses of ionizing radiation (LDIR) (Interventional Radiology and Cardiology, Radiation Oncology, and Nuclear Medicine) and non-exposed. Personal dose equivalent (from last year and cumulative), plasma antioxidant markers (total antioxidant capacity, extracellular superoxide dismutase activity, and glutathione/oxidized glutathione ratio), oxidative stress markers (nitrites and nitrates, and lipid peroxidation) and dietary intake (antioxidant capacity using ORAC values) were collected and analyzed from 28 non-exposed healthcare workers and 42 healthcare workers exposed to LDIR. Hospital staff exposed to LDIR presented a redox imbalance in blood that seems to correlate with dose. Workers from the Nuclear Medicine Unit were the most affected group with the lowest value of plasma antioxidant response and the highest value of plasma thiobarbituric acid reactive substances, TBARS (indicator of lipid peroxidation) of all four groups. Cumulative personal dose equivalent positively correlated with nitrites and negatively correlated with total antioxidant capacity in blood. The diet of healthcare workers from Nuclear Medicine Unit had higher ORAC values than the diet of non-exposed. Therefore, occupational exposure to LDIR, especially for the Nuclear Medicine Unit, seems to produce an imbalanced redox status in blood that would correlate with cumulative personal dose equivalent. Full article

Alzheimer’s disease (AD) is the most common type of dementia. AD involves major pathologies such as amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain. During the progression of AD, microglia can be polarized from anti-inflammatory M2 to pro-inflammatory M1 phenotype. The activation of triggering receptor expressed on myeloid cells 2 (TREM2) may result in microglia phenotype switching from M1 to M2, which finally attenuated Aβ deposition and memory loss in AD. Low-dose ionizing radiation (LDIR) is known to ameliorate Aβ pathology and cognitive deficits in AD; however, the therapeutic mechanisms of LDIR against AD-related pathology have been little studied. First, we reconfirm that LDIR (two Gy per fraction for five times)-treated six-month 5XFAD mice exhibited (1) the reduction of Aβ deposition, as reflected by thioflavins S staining, and (2) the improvement of cognitive deficits, as revealed by Morris water maze test, compared to sham-exposed 5XFAD mice. To elucidate the mechanisms of LDIR-induced inhibition of Aβ accumulation and memory loss in AD, we examined whether LDIR regulates the microglial phenotype through the examination of levels of M1 and M2 cytokines in 5XFAD mice. In addition, we investigated the direct effects of LDIR on lipopolysaccharide (LPS)-induced production and secretion of M1/M2 cytokines in the BV-2 microglial cells. In the LPS- and LDIR-treated BV-2 cells, the M2 phenotypic marker CD206 was significantly increased, compared with LPS- and sham-treated BV-2 cells. Finally, the effect of LDIR on M2 polarization was confirmed by detection of increased expression of TREM2 in LPS-induced BV2 cells. These results suggest that LDIR directly induced phenotype switching from M1 to M2 in the brain with AD. Taken together, our results indicated that LDIR modulates LPS- and Aβ-induced neuroinflammation by promoting M2 polarization via TREM2 expression, and has beneficial effects in the AD-related pathology such as Aβ deposition and memory loss. Full article

Alzheimer’s disease (AD) is the most common cause of dementia. The neuropathological features of AD include amyloid-β (Aβ) deposition and hyperphosphorylated tau accumulation. Although several clinical trials have been conducted to identify a cure for AD, no effective drug or treatment has been identified thus far. Recently, the potential use of non-pharmacological interventions to prevent or treat AD has gained attention. Low-dose ionizing radiation (LDIR) is a non-pharmacological intervention which is currently being evaluated in clinical trials for AD patients. However, the mechanisms underlying the therapeutic effects of LDIR therapy have not yet been established. In this study, we examined the effect of LDIR on Aβ accumulation and Aβ-mediated pathology. To investigate the short-term effects of low–moderate dose ionizing radiation (LMDIR), a total of 9 Gy (1.8 Gy per fraction for five times) were radiated to 4-month-old 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD, and then sacrificed at 4 days after last exposure to LMDIR. Comparing sham-exposed and LMDIR-exposed 5XFAD mice indicated that short-term exposure to LMDIR did not affect Aβ accumulation in the brain, but significantly ameliorated synaptic degeneration, neuronal loss, and neuroinflammation in the hippocampal formation and cerebral cortex. In addition, a direct neuroprotective effect was confirmed in SH-SY5Y neuronal cells treated with Aβ_1–42 (2 μM) after single irradiation (1 Gy). In BV-2 microglial cells exposed to Aβ and/or LMDIR, LMDIR therapy significantly inhibited the production of pro-inflammatory molecules and activation of the nuclear factor-kappa B (NF-κB) pathway. These results indicate that LMDIR directly ameliorated neurodegeneration and neuroinflammation in vivo and in vitro. Collectively, our findings suggest that the therapeutic benefits of LMDIR in AD may be mediated by its neuroprotective and anti-inflammatory effects. Full article

(1) Background: Emerging interest of physicians to use adipose-derived stem cells (ADSCs) for regenerative therapies and the fact that low-dose irradiation (LD-IR ≤ 0.1 Gy) has been reported to enhance the proliferation of several human normal and bone-marrow stem cells, but not that of tumor cells, lead to the idea of improving stem cell therapies via low-dose radiation. Therefore, the aim of this study was to investigate unwanted side effects, as well as proliferation-stimulating mechanisms of LD-IR on ADSCs. (2) Methods: To avoid donor specific effects, ADSCs isolated from mamma reductions of 10 donors were pooled and used for the radiobiological analysis. The clonogenic survival assay was used to classify the long-term effects of low-dose radiation in ADSCs. Afterwards, cytotoxicity and genotoxicity, as well as the effect of irradiation on proliferation of ADSCs were investigated. (3) Results: LD (≤ 0.1 Gy) of ionizing radiation promoted the proliferation and survival of ADSCs. Within this dose range neither geno- nor cytotoxic effects were detectable. In contrast, greater doses within the dose range of >0.1–2.0 Gy induced residual double-strand breaks and reduced the long-term survival, as well as the proliferation rate of ADSCs. (4) Conclusions: Our data suggest that ADSCs are resistant to LD-IR. Furthermore, LD-IR could be a possible mediator to improve approaches of stem cells in the field of regenerative medicine. Full article

Exposure to ionizing radiation (IR) is inevitable to humans in real-life scenarios; the hazards of IR primarily stem from its mutagenic, carcinogenic, and cell killing ability. For many decades, extensive research has been conducted on the human cell responses to IR delivered at a low dose/low dose (LD) rate. These studies have shown that the molecular-, cellular-, and tissue-level responses are different after low doses of IR (LDIR) compared to those observed after a short-term high-dose IR exposure (HDIR). With the advent of high-throughput technologies in the late 1990s, such as DNA microarrays, changes in gene expression have also been found to be ubiquitous after LDIR. Very limited subset of genes has been shown to be consistently up-regulated by LDIR, including CDKN1A. Further research on the biological effects and mechanisms induced by IR in human cells demonstrated that the molecular and cellular processes, including transcriptional alterations, activated by LDIR are often related to protective responses and, sometimes, hormesis. Following LDIR, some distinct responses were observed, these included bystander effects, and adaptive responses. Changes in gene expression, not only at the level of mRNA, but also miRNA, have been found to crucially underlie these effects having implications for radiation protection purposes. Full article

The biological effects of low-dose ionizing radiation (LDIR) exposure in humans are not comprehensively understood, generating a high degree of controversy in published literature. The earliest stages of human development are known to be among the most sensitive to stress exposures, especially genotoxic stresses. However, the risks stemming from exposure to LDIR, particularly within the clinical diagnostic relevant dose range, have not been directly evaluated in human embryonic stem cells (hESCs). Here, we describe the dynamics of the whole genome transcriptional responses of different hESC lines to both LDIR and, as a reference, high-dose IR (HDIR). We found that even doses as low as 0.05 Gy could trigger statistically significant transient changes in a rather limited subset of genes in all hESCs lines examined. Gene expression signatures of hESCs exposed to IR appear to be highly dose-, time-, and cell line-dependent. We identified 50 genes constituting consensus gene expression signature as an early response to HDIR across all lines of hESC examined. We observed substantial differences in biological pathways affected by either LDIR or HDIR in hESCs, suggesting that the molecular mechanisms underpinning the responses of hESC may fundamentally differ depending on radiation doses. Full article